Yasmin Ahmad
DRDO, Peptide and Proteomics Divison, Department Member
- I have been working as a staff scientist in the domain of Biomarker Discovery for their clinical application for over... moreI have been working as a staff scientist in the domain of Biomarker Discovery for their clinical application for over ten years. Being a part of DIPAS (A premiere institute of DRDO) which leads the clinical research during extreme environmental conditions, I was fortunate to investigate the potentials of human blood plasma for the discovery of putative biomarkers that could benefit clinicians in deciding disease susceptibility and disease progression.edit
High altitude acclimatization and disease have been the centerpiece of investigations concerning human health at high altitude. Almost all investigations have focused on either understanding and ameliorating high altitude disease or... more
High altitude acclimatization and disease have been the centerpiece of investigations concerning human health at high altitude. Almost all investigations have focused on either understanding and ameliorating high altitude disease or finding better methods of acclimatization/training at high altitude. The aspect of altitude de-induction/de-acclimatization has remained clouded despite the fact that it was documented since the first decade of twentieth century. A few recent studies, particularly in China, have stated unanimously that high altitude de-acclimatization involved multiple observable clinical symptoms ranging from headache to abdominal distention. These symptoms have been collectively referred to as “high altitude de-acclimatization syndrome” (HADAS). However, computational omics and network biology centric investigations concerning HADAS are nascent. In this study, we focus on the quantitative proteo-informatics, especially network biology, of human plasma proteome in indiv...
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Background and Aim: The boutade of coronavirus disease-2019(COVID-19) has a striking impact on the worldwide healthcare system within a very short period of time. Availability of a large number of clinical data on SARS-CoV-2, conventional... more
Background and Aim: The boutade of coronavirus disease-2019(COVID-19) has a striking impact on the worldwide healthcare system within a very short period of time. Availability of a large number of clinical data on SARS-CoV-2, conventional precautionary majors, and treatment strategies with the existing therapeutic antiviral drug molecules are also failing to control progression and disease transmission among the population. Hence, we implemented pharmacoinformatics approaches to facilitate the drug discovery process by repurposing naturally available therapeutic molecules as an effective intervention. Experimental Procedure: The major phenolic derivatives of Silybum marianum(Milk thistle) have been identified and investigated for ADME(Absorption, Distribution, Metabolism and Excretion)/tox properties. Co-crystallized structure of three major proteins(i.e. Main protease, RNA binding domain of nucleocapsid phosphoprotein and Spike receptor binding domain) from SARS-CoV-2 investigated ...
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Exposure to high altitude induces physiological responses due to hypoxia. Lungs being at the first level to face the alterations in oxygen levels are critical to counter and balance these changes. Studies have been done analysing... more
Exposure to high altitude induces physiological responses due to hypoxia. Lungs being at the first level to face the alterations in oxygen levels are critical to counter and balance these changes. Studies have been done analysing pulmonary proteome alterations in response to exposure to hypobaric hypoxia. However, such studies have reported the alterations at specific time points and do not reflect the gradual proteomic changes. These studies also identify the various biochemical pathways and responses induced after immediate exposure and the resolution of these effects in challenge to hypobaric hypoxia. In the present study, using 2-DE/MS approach, we attempt to resolve these shortcomings by analysing the proteome alterations in lungs in response to different durations of exposure to hypobaric hypoxia. Our study thus highlights the gradual and dynamic changes in pulmonary proteome following hypobaric hypoxia. For the first time, we also report the possible consideration of SULT1A1,...
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Research Interests: Computational Biology, Biology, Proteomics, Medicine, Multidisciplinary, and 15 moreWestern blotting, Anoxia, Animals, Gene ontology, PLoS one, Air Pressure, Rats, Hypobaric Chamber, Analysis of Variance, Time Factors, Western blot, Biological markers, Two-Dimensional Gel Electrophoresis, Blood Proteins, and Gene Expression Regulation
Extended exposure to low pO2 has multiple effects on signaling cascades. Despite multiple exploratory studies, omics studies elucidating the signaling cascades essential for surviving extended low pO2 exposures are lacking. In this study,... more
Extended exposure to low pO2 has multiple effects on signaling cascades. Despite multiple exploratory studies, omics studies elucidating the signaling cascades essential for surviving extended low pO2 exposures are lacking. In this study, we simulated low pO2 (PB = 40 kPa; 7620 m) exposure in male Sprague-Dawley rats for 3, 7 and 14 days. Redox stress assays and proteomics based network biology were performed using lungs and plasma. We observed that redox homeostasis was achieved after day 3 of exposure. We investigated the causative events for this. Proteo-bioinformatics analysis revealed STAT3 to be upstream of lung cytoskeletal processes and systemic lipid metabolism (RXR) derived inflammatory processes, which were the key events. Thus, during prolonged low pO2 exposure, particularly those involving slowly decreasing pressures, redox homeostasis is achieved but energy metabolism is perturbed and this leads to an immune/inflammatory signaling impetus after third day of exposure. We found that an interplay of lung cytoskeletal elements, systemic energy metabolism and inflammatory proteins aid in achieving redox homeostasis and surviving extended low pO2 exposures. Qualitative perturbations to cytoskeletal stability and innate immunity/inflammation were also observed during extended low pO2 exposure in humans exposed to 14,000 ft for 7, 14 and 21 days.
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Background Exposure to high-altitude leads to two outcomes: acclimation and mal-acclimation leading to high-altitude illnesses (HAIs). Acclimation to altitude actively negates HAIs like acute mountain sickness, high-altitude pulmonary... more
Background Exposure to high-altitude leads to two outcomes: acclimation and mal-acclimation leading to high-altitude illnesses (HAIs). Acclimation to altitude actively negates HAIs like acute mountain sickness, high-altitude pulmonary and cerebral edemas. Although HAIs have been scrutinized, acclimation has remained only empirically understood with minimal knowledge of it at molecular level in an organism. Methods In this study, we investigated (using ELISA) and statistically evaluated the trendlines of various hypoxia-responsive plasma proteins' levels, reported significantly perturbed in multiple previous studies, in individuals (male; n=20) exposed to 3520 m at high-altitude day 1 (HAD1), HAD4 and HAD7L and to 4420 m at HAD7H, HAD30 and HAD120. Findings We observed that thioredoxin (Trx), glutathione peroxidase 3 (GPx-3) and apolipoprotein AI (Apo-AI) are statistically robust markers to assess acclimation across the exposure duration while sulfotransferase 1A1 (ST1A1) is a...
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Research Interests: Biology, Inflammation, Medicine, Multidisciplinary, Humans, and 15 moreAnoxia, Transthyretin, Male, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, PLoS one, Chemical Precipitation, Adult, Altitude, Haptoglobin, Proteome, Blood Proteins, immunoglobulin G, Gene Expression Regulation, Gene expression profiling, and Serum albumin
Research Interests: Genetics, Biology, Inflammation, Medicine, Apolipoproteins, and 15 moreHumans, Male, Apolipoprotein B, Altitude Sickness, Biological markers, Proteome analysis, Acute Phase Proteins, Haptoglobin, Proteome, Enzyme Linked Immunosorbent Assay, Clusterin, Case Control Studies, Pulmonary Edema, Blood Plasma, and Inflammatory response
Key PointsHypoxia induces altered platelet proteome/reactivity, which correlates with a prothrombotic phenotype. CAPNS1-dependent calpain activity in platelet activation cascade is associated with hypoxia-induced thrombogenesis.
Research Interests: Biology, Medicine, Platelet, Humans, Anoxia, and 15 moreAnimals, Blood, Male, Platelet activation mechanism, Phenotype, Clinical Sciences, Calpain, Rats, Altitude Sickness, Adult, Proteome, thrombophilia, Blood platelets, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
Millions of people worldwide visit, live, or work in the hypoxic environment encountered at high altitudes and it is important to understand the biomolecular responses to this stress. This would help design mitigation strategies for High... more
Millions of people worldwide visit, live, or work in the hypoxic environment encountered at high altitudes and it is important to understand the biomolecular responses to this stress. This would help design mitigation strategies for High Altitude Illnesses (HAIs). Inspite of a number of studies spanned over 100 years, complex mechanisms controlling acclimatization to hypoxia remain largely unknown. Some biomolecules, though, have been proposed as potential diagnostic, therapeutic and predictive markers for HA stress. HighAltitudeOmicsDB is a unique resource that provides a comprehensive, curated, user- friendly and detailed compilation of various genes/proteins which have been experimentally validated to be associated with various HA conditions; their Protein Protein Interactions (PPI) and Gene Ontology (GO) semantic similarities. For each database entry, HighAltitudeOmicsDB stores the level of regulation (up/down-regulation), fold change, control (low landers or high landers), dura...
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Hypoxia, particularly hypobaric hypoxia, is a multifaceted entity which includes certain molecular, patho-physiological and biochemical aspects. Any single aspect in itself cannot help us elucidate hypobaric hypoxia in its entirety. We... more
Hypoxia, particularly hypobaric hypoxia, is a multifaceted entity which includes certain molecular, patho-physiological and biochemical aspects. Any single aspect in itself cannot help us elucidate hypobaric hypoxia in its entirety. We observed three crucial lacunae within the existing literature. These include a lack of high-throughput investigations into redox PTMs, particularly NO-based PTMs; a prophylactic supplement with proven efficacy and safety which doesn’t involve medical supervision and is not contraindicated in hepatic, renal and cardiac insufficiencies; and a clinically validated rodent model of HAPE without any genetic/pharmacological manipulations. In the present study, we present an antagonistic interplay between nitrosylation and carbonylation which shows an additional NO-based network that is active in acclimatised individuals. Then we present a micronised aqueous suspension of silymarin which is efficacious at low doses in providing antioxidant, anti-inflammatory ...
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Intermittent hypoxia, initially associated with adverse effects of sleep apnea, has now metamorphosed into a module for improved sports performance. The regimen followed for improved sports performance is milder intermittent hypoxic... more
Intermittent hypoxia, initially associated with adverse effects of sleep apnea, has now metamorphosed into a module for improved sports performance. The regimen followed for improved sports performance is milder intermittent hypoxic training (IHT) as compared to chronic and severe intermittent hypoxia observed in sleep apnea. Although several studies have indicated the mechanism and enough data on physiological parameters altered by IH is available, proteome perturbations remain largely unknown. Altitude induced hypobaric hypoxia is known to require acclimatization as it causes systemic redox stress and inflammation in humans. In the present study, a short IHT regimen consisting of previously reported physiologically beneficial FIO2 levels of 13.5% and 12% was administered to human subjects. These subjects were then airlifted to altitude of 3500 m and their plasma proteome along with associated redox parameters were analyzed on days 4 and 7 of high altitude stay. We observed that re...
The repercussions of hypobaric hypoxia are dependent upon two factors: time and intensity of exposure. The effects of intensity i.e. variation of altitude are yet unknown although it is a significant factor in terms of acclimatization... more
The repercussions of hypobaric hypoxia are dependent upon two factors: time and intensity of exposure. The effects of intensity i.e. variation of altitude are yet unknown although it is a significant factor in terms of acclimatization protocols. In this study we present the effects of acute (24 h) exposure to high (10,000 ft), very high (15,000 ft) and extreme altitude (25,000 ft) zones on lung and plasma using semi-quantitative redox specific transcripts and quantitative proteo-bioinformatics workflow in conjunction with redox stress assays. Our findings indicate that very high altitude exposure elicits systemic redox homeostatic processes due to failure of lung redox homeostasis without causing mortality. We also document a rapid acclimatization protocol causing a shift from 0 to 100% survival at 25,000 ft in male SD rats upon rapid induction. Finally we posit the various processes involved and the plasma proteins that can be used to ascertain the acclimatization status of an indi...
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Background: Hypoxia is a pathophysiological condition which arises due to low oxygen concentration in conditions like cardiovascular diseases, inflammation, ascent to higher altitude, malignancies, deep sea diving, prenatal birth, etc. A... more
Background: Hypoxia is a pathophysiological condition which arises due to low oxygen concentration in conditions like cardiovascular diseases, inflammation, ascent to higher altitude, malignancies, deep sea diving, prenatal birth, etc. A number of microRNAs (miRNAs), Transcription Factors (TFs) and genes have been studied separately for their role in hypoxic adaptation and controlling cell-cycle progression and apoptosis during this stress. Objective: We hypothesize that miRNAs and TFs may act in conjunction to regulate a multitude of genes and play a crucial and combinatorial role during hypoxia-stress-responses and associated cellcycle control mechanisms. Methods: We collected a comprehensive and non-redundant list of human hypoxia-responsive miRNAs (also known as hypoxiamiRs). Their experimentally validated gene-targets were retrieved from various databases and a comprehensive hypoxiamiR-gene regulatory network was built. Results: Functional characterization and pathway enrichmen...
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Identification of molecular signatures having key roles in hypobaric hypoxia by analysing the salivary proteome. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate,... more
Identification of molecular signatures having key roles in hypobaric hypoxia by analysing the salivary proteome. Saliva holds a promising future in the search for new clinical biomarkers that are easily accessible, less complex, accurate, and cost effective as well as being non-invasive. We employed qualitative proteomics approach to develop discriminatory biomarker signatures from human saliva exposed to hypobaric hypoxia. Salivary proteins were analyzed and compared between age-matched healthy subjects exposed to high altitude (∼13700 ft) for seven days (HAD7) with control subjects at sea level (Normoxia) by using 2-Dimensional gel electrophoresis/Mass Spectrometry approach. Several proteins with significant differential expression were found. The up-regulated proteins were apoptosis inducing factor-2, cystatin S, cystatin SN and carbonic anhydrase 6. The down regulated proteins were polymeric immunoglobulin receptor, alpha-enolase and prolactin-inducible protein. Further confirmation of the altered proteins such as alpha enolase, carbonic anhydrase 6, prolactin-inducible protein, apoptosis inducing factor 2, cystatin S and cystatin SN were performed using immunoblotting. The expression patterns of the selected proteins observed by immunoblot were in concurrence with 2-Dimesional gel electrophoresis results, therefore affirming the authenticity of the proteomic investigation. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of hypobaric hypoxia induced effects. It is highly feasible to turn these biomarkers into an applicable clinical test after large scale validation.
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Hypoxia, especially altitude associated hypoxia is known to cause severe physiological alterations and life-threatening conditions. Impaired redox balance along with oxidative stress, protein carbonylation and instigation of apoptotic... more
Hypoxia, especially altitude associated hypoxia is known to cause severe physiological alterations and life-threatening conditions. Impaired redox balance along with oxidative stress, protein carbonylation and instigation of apoptotic events are common sub-cellular events that follow the hypoxic insult. The role of nitric oxide (NO) is very dynamic and versatile in preventing the ill effects of hypoxia vis-a-vis reacting with oxidative species and causing protein nitrosylation. Although several mechanisms of NO-mediated cytoprotection are known during hypoxic insult, limited pieces of evidence are available to support the relationship between two downstream events of oxidative stress, protein carbonylation (caused by carbonyl; CO radical) and protein nitrosylation/nitration (caused by NO/peroxynitrite; ONOO radical). In this study, we investigated an entirely new aspect of NO protection in hypoxia involving crosstalk between carbonylation and nitrosylation. Using standard NO inhibit...
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Lack of zero side-effect, prescription-less prophylactics and diagnostic markers of acclimatization status lead to many suffering from high altitude illnesses. Although not fully translated to the clinical setting, many strategies and... more
Lack of zero side-effect, prescription-less prophylactics and diagnostic markers of acclimatization status lead to many suffering from high altitude illnesses. Although not fully translated to the clinical setting, many strategies and interventions are being developed that are aimed at providing an objective and tangible answer regarding the acclimatization status of an individual as well as zero side-effect prophylaxis that is cost-effective and does not require medical supervision. This short review brings together the twin problems associated with high-altitude acclimatization, i.e. acclimatization status and zero side-effect, easy-to-use prophylaxis, for the reader to comprehend as cogs of the same phenomenon. We describe current research aimed at preventing all the high-altitude illnesses by considering them an assault on redox and energy homeostasis at the molecular level. This review also entails some proteins capable of diagnosing either acclimatization or high-altitude illn...
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Computational biology has opened a gateway to omics data analysis and shifted the focus from molecules to systemic molecular networks in the domain of hypobaric hypoxia (HH). Yet there are no meta-analytical investigations circum-venting... more
Computational biology has opened a gateway to omics data analysis and shifted the focus from molecules to systemic molecular networks in the domain of hypobaric hypoxia (HH). Yet there are no meta-analytical investigations circum-venting constraints like organism (rat/human), HH exposure conditions (acute/chronic) and the tissues that can be investigated simultaneously in the realm of wet-lab experiments. We analyzed 154 DE proteins upon HH exposure using IPA tool, without the constraint of using a single organism or tissue type, to determine the most significant pathways and networks that are perturbed across a range of HH conditions RESULTS: : We found Acute phase Response Signaling, FXR/RXR Activation, LXR/RXR Activation, Clathrin-mediated endocytosis signaling, Mitochondrial Dysfunction, Production of Nitric Oxide & ROS in Macrophages and Integrin Signaling to be the most significant universally perturbed pathways. Unique protein-function relationships have also been highlighted...
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ABSTRACT
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A simple and sensitive kinetic spectrophotometric method for the determination of metoprolol tartrate has been proposed. In the developed approach analyte reacts with ninhydrin in N,N'-dimethylformamide (DMF) medium at 95′... more
A simple and sensitive kinetic spectrophotometric method for the determination of metoprolol tartrate has been proposed. In the developed approach analyte reacts with ninhydrin in N,N'-dimethylformamide (DMF) medium at 95′ 1°C to produce blue colour. ...
Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and... more
Hypobaric hypoxia elicits several patho-physiological manifestations, some of which are known to be lethal. Among various molecular mechanisms proposed so far, perturbation in redox state due to imbalance between radical generation and antioxidant defence is promising. These molecular events are also related to hypoxic status of cancer cells and therefore its understanding has extended clinical advantage beyond high altitude hypoxia. In present study, however, the focus was to understand and propose a model for rapid acclimatization of high altitude visitors to enhance their performance based on molecular changes. We considered using simulated hypobaric hypoxia at some established thresholds of high altitude stratification based on known physiological effects. Previous studies have focused on the temporal aspect while overlooking the effects of varying pO2 levels during exposure to hypobaric hypoxia. The pO2 levels, indicative of altitude, are crucial to redox homeostasis and can be...
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Despite its extraordinary antioxidant capacity, the clinical usage of silymarin has remained restricted to amelioration of hepatic pathology. Perhaps its low bioavailability and uneven bio-distribution, owing to its poor aqueous... more
Despite its extraordinary antioxidant capacity, the clinical usage of silymarin has remained restricted to amelioration of hepatic pathology. Perhaps its low bioavailability and uneven bio-distribution, owing to its poor aqueous solubility, are two main causes that have dampened the clinical applicability and scope of this preparation. We took these two challenges and suggested an unexplored application of silymarin. Apart from liver, two of the most susceptible vital organs at the highest risk of oxidative stress are brain and lung, especially during reduced oxygen saturation (hypoxia) at anatomical level. Hypoxia causes excess generation of radicals primarily in the lungs as it is the first organ at the interphase of atmosphere and organism making it the most prone and vulnerable to oxidative stress and the first responder against hypobaric hypoxia. As our first objective, we improved the silymarin formulation by restricting its size to the lower threshold and then successfully tested the prophylactic and therapeutic action in rat lung challenged with simulated hypobaric hypoxia. After dose optimization, we observed that 50mg/kg BW silymarin as size restricted and homogenous aqueous suspension successfully minimized the reactive oxygen species and augmented the antioxidant defense by significant upregulation of catalase and superoxide dismutase and reduced glutathione. Moreover, the well-established hypoxia markers and proteins related to hypoxia adaptability, hif1a and VEGF were differentially regulated conferring significant reduction in the inflammation caused by hypobaric hypoxia. We therefore report,the unexplored potential benefits of silymarin for preventing high altitude associated pathophysiology further paving its road to clinical trials.
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Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level... more
Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased 'statistical co-expression networks' generated utilizing temporal, differential transcriptome signatures of hippocampus-centrally involved in regulating cognition-implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment.
Several studies have supported the hypoxia mimetic roles and cytoprotective properties of cobalt chloride in vitro and in vivo. However, a clear understanding of biological process-based mechanism that integrates the available information... more
Several studies have supported the hypoxia mimetic roles and cytoprotective properties of cobalt chloride in vitro and in vivo. However, a clear understanding of biological process-based mechanism that integrates the available information remains unknown. This study was aimed to explore the potential mechanism of cobalt chloride deciphering its benefits and well-known physiological challenge caused by hypobaric hypoxia that reportedly affects nearly 24 % of the global population. In order to explore the mechanism of CoCl2, we used global proteomic and systems biology approach in rat model to provide a deeper insight into molecular mechanisms of preconditioning. Furthermore, key conclusions were drawn based on biological network analysis and their enrichment with ontological overlaps. The study was further strengthened by consistent identification of validation of proteins using immunoblotting. CoCl2-pretreated animals exposed to hypoxia showed two significant networks, one lipid met...
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Research Interests: Genetics, Inflammation, Sea Level, Inflammatory Immune Response, Apolipoproteins, and 16 moreHumans, Male, Time of Flight, apolipoprotein A-I, Altitude Sickness, Western blot, Biological markers, Proteome analysis, Acute Phase Proteins, Two-Dimensional Gel Electrophoresis, Two dimensional Gel Electrophoresis, Proteome, Enzyme Linked Immunosorbent Assay, Case Control Studies, Pulmonary Edema, and Blood Plasma
Hypobaric hypoxia causes complex changes in the expression of genes, including stress related genes and corresponding proteins that are necessary to maintain homeostasis. Whereas most prior studies focused on single proteins, newer... more
Hypobaric hypoxia causes complex changes in the expression of genes, including stress related genes and corresponding proteins that are necessary to maintain homeostasis. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of complex and dynamic changes that occur during the hypobaric hypoxia. In this study we investigated the temporal plasma protein alterations of rat induced by hypobaric hypoxia at a simulated altitude of 7620 m (25,000 ft, 282 mm Hg) in a hypobaric chamber. Total plasma proteins collected at different time points (0, 6, 12 and 24 h), separated by two-dimensional electrophoresis (2-DE) and identified using matrix assisted laser desorption ionization time of flight (MALDI-TOF/TOF). Biological processes that were enriched in the plasma proteins during hypobaric hypoxia were identified using Gene Ontology (GO) analysis. According to their properties and obvious alte...
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Exposure to high altitude induces physiological responses due to hypoxia. Lungs being at the first level to face the alterations in oxygen levels are critical to counter and balance these changes. Studies have been done analysing... more
Exposure to high altitude induces physiological responses due to hypoxia. Lungs being at the first
level to face the alterations in oxygen levels are critical to counter and balance these changes.
Studies have been done analysing pulmonary proteome alterations in response to exposure to
hypobaric hypoxia. However, such studies have reported the alterations at specific time points and
do not reflect the gradual proteomic changes. These studies also identify the various biochemical
pathways and responses induced after immediate exposure and the resolution of these effects
in challenge to hypobaric hypoxia. In the present study, using 2-DE/MS approach, we attempt to
resolve these shortcomings by analysing the proteome alterations in lungs in response to different
durations of exposure to hypobaric hypoxia. Our study thus highlights the gradual and dynamic
changes in pulmonary proteome following hypobaric hypoxia. For the first time, we also report the
possible consideration of SULT1A1, as a biomarker for the diagnosis of high altitude pulmonary
edema (HAPE). Higher SULT1A1 levels were observed in rats as well as in humans exposed to high
altitude, when compared to sea-level controls. This study can thus form the basis for identifying
biomarkers for diagnostic and prognostic purposes in responses to hypobaric hypoxia.
level to face the alterations in oxygen levels are critical to counter and balance these changes.
Studies have been done analysing pulmonary proteome alterations in response to exposure to
hypobaric hypoxia. However, such studies have reported the alterations at specific time points and
do not reflect the gradual proteomic changes. These studies also identify the various biochemical
pathways and responses induced after immediate exposure and the resolution of these effects
in challenge to hypobaric hypoxia. In the present study, using 2-DE/MS approach, we attempt to
resolve these shortcomings by analysing the proteome alterations in lungs in response to different
durations of exposure to hypobaric hypoxia. Our study thus highlights the gradual and dynamic
changes in pulmonary proteome following hypobaric hypoxia. For the first time, we also report the
possible consideration of SULT1A1, as a biomarker for the diagnosis of high altitude pulmonary
edema (HAPE). Higher SULT1A1 levels were observed in rats as well as in humans exposed to high
altitude, when compared to sea-level controls. This study can thus form the basis for identifying
biomarkers for diagnostic and prognostic purposes in responses to hypobaric hypoxia.
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The oxygen compromised environments such as high altitude, air travel, sports and solid tumors have been suggested to be prothrombotic. Despite the indispensable role of platelets in thrombus formation, the studies linking hypoxia,... more
The oxygen compromised environments such as high altitude, air travel, sports and solid tumors
have been suggested to be prothrombotic. Despite the indispensable role of platelets in thrombus
formation, the studies linking hypoxia, platelet reactivity and thrombus formation are limited. In
the present study, platelet proteome/reactivity was analyzed to elucidate the acute hypoxia
induced prothrombotic phenotype. Rats exposed to acute simulated hypoxia (282 torr/ 8%
oxygen) demonstrated a decreased bleeding propensity and increased platelet reactivity.
Proteomic analysis of hypoxic platelets revealed 27 differentially expressed proteins including
those involved in coagulation. Among these proteins, calpain small subunit-1(CAPNS1), a 28
kDa regulatory component for calpain function was significantly upregulated under hypoxic
conditions. Moreover, intraplatelet Ca2+ level and platelet calpain activity were also found to be
in accordance with CAPNS1 expression. The inhibition of calpain activity demonstrated reversal
of the hypoxia induced platelet hyperreactivity. The prothrombotic role for calpain was further
confirmed by an in vivo model of hypoxia-induced thrombosis. Interestingly, patients who
developed thrombosis while placed at extreme altitude had elevated plasma calpain activities and
increased sP-selectin level. In summary, this study for the first time suggests that augmented
calpain activity is associated with increased incidence of thrombosis under hypoxic
environments.
have been suggested to be prothrombotic. Despite the indispensable role of platelets in thrombus
formation, the studies linking hypoxia, platelet reactivity and thrombus formation are limited. In
the present study, platelet proteome/reactivity was analyzed to elucidate the acute hypoxia
induced prothrombotic phenotype. Rats exposed to acute simulated hypoxia (282 torr/ 8%
oxygen) demonstrated a decreased bleeding propensity and increased platelet reactivity.
Proteomic analysis of hypoxic platelets revealed 27 differentially expressed proteins including
those involved in coagulation. Among these proteins, calpain small subunit-1(CAPNS1), a 28
kDa regulatory component for calpain function was significantly upregulated under hypoxic
conditions. Moreover, intraplatelet Ca2+ level and platelet calpain activity were also found to be
in accordance with CAPNS1 expression. The inhibition of calpain activity demonstrated reversal
of the hypoxia induced platelet hyperreactivity. The prothrombotic role for calpain was further
confirmed by an in vivo model of hypoxia-induced thrombosis. Interestingly, patients who
developed thrombosis while placed at extreme altitude had elevated plasma calpain activities and
increased sP-selectin level. In summary, this study for the first time suggests that augmented
calpain activity is associated with increased incidence of thrombosis under hypoxic
environments.