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    Rosaria Scudiero

    Iron is an essential element for metabolic processes intrinsic to life, but the properties that make iron a necessity also make it potentially deleterious. To avoid harm, iron homeostasis is achieved through iron transport, storage and... more
    Iron is an essential element for metabolic processes intrinsic to life, but the properties that make iron a necessity also make it potentially deleterious. To avoid harm, iron homeostasis is achieved through iron transport, storage and regulatory proteins. The functions of some of these molecules are well described, for example transferrin and ferritin, whereas the roles of others remain unclear. The past decade has seen the identification of new molecules involved in iron metabolism, such as divalent metal transporter-1, and hepcidin. The present review aims at surveying the studies carried out on some of the most important genes involved in transport and storage of iron in Antarctic Notothenioidei, a dominating fish group endowed of a number of striking adaptive characters, including reduced (or absence of) hematocrit. This unique peculiarity among vertebrates makes this fish group a suitable system to studying the relationship between hemoglobin and iron metabolism and to understanding the adaptive changes occurred in Antarctic fish metabolism during their evolution to avoid the deleterious effects of iron overload in the absence of hemoglobin. The results summarised here indicate that the loss of hemoglobin in the most specialized group of Antarctic notothenioids, belonging to the Channychthyidae family, is accompanied by remodulation of the iron metabolism.
    The possible role of metallothionein (MT) in metal homeostasis has been investigated in growing oocytes and eggs of the lizard Podarcis sicula. Chromatographic analysis does not reveal the presence of MT in both ovary and eggs, the only... more
    The possible role of metallothionein (MT) in metal homeostasis has been investigated in growing oocytes and eggs of the lizard Podarcis sicula. Chromatographic analysis does not reveal the presence of MT in both ovary and eggs, the only metal-binding proteins detected being represented by high molecular mass components. De novo synthesis of MT could be observed in the ovary of cadmium-treated lizards. A cDNA encoding MT was obtained from the liver of P. sicula by RT-PCR followed by a RACE strategy, using primers designed on consensus motifs of vertebrate MT. In spite of the lack of MT in the ovary of untreated animals, Northern blot analysis demonstrates that the maternal untranslated MT transcript is expressed constitutively in the ovary in all the periods of the ovarian cycle. MT mRNA content increases during the oocyte growth, reaching the highest level in ovulated eggs, concomitantly with the accumulation of zinc and copper. Our findings suggest that maternal MT mRNA accumulates in the egg and is translated sometime during development to cope with the future needs of the growing embryo. The appearance of MT after cadmium treatment suggests that the block that makes the oocytarian MT mRNA untranslatable is removed by the metal.
    Organisms living in the Southern Ocean are exposed to strong environmental constraints, especially temperature. The Perciform suborder Notothenioidei, today largely endemic to the Antarctic, has developed numerous cold-adapted characters.... more
    Organisms living in the Southern Ocean are exposed to strong environmental constraints, especially temperature. The Perciform suborder Notothenioidei, today largely endemic to the Antarctic, has developed numerous cold-adapted characters. The most striking peculiarity of this group of fish is the drastic reduction of hemoglobin content in their blood. This condition gives rise to a low metabolic demand of iron. Recently, we have undertaken a study to add new insights on iron metabolism in hemoglobinless fish. By taking advantage to our previous studies on transferrins from Antarctic Notothenioids, in this article we compared the evolutionary properties of these sequences to those from other fish groups and mammals. Our findings based on analysis of dN/dS ratio and on the results of the relative rate ratio test suggest that the transferrin gene has undergone positive selection in fish but not in mammals. The results of type I functional divergence provide statistical evidence for shifted evolutionary rate after speciation. Finally, when superimposed onto the three-dimensional structure of transferrin, the sites identified as responsible of the divergence in Notothenioids appear to cluster preferentially at non-iron binding locations, occupying surface locations that might affect the rate of iron binding and/or release in a cold environment.
    Pharmaceuticals are a class of emerging environmental contaminants. Gadolinium (Gd) is a metal of the lanthanide series of the elements whose chelates are commonly employed as contrast agents for magnetic resonance imaging, and... more
    Pharmaceuticals are a class of emerging environmental contaminants. Gadolinium (Gd) is a metal of the lanthanide series of the elements whose chelates are commonly employed as contrast agents for magnetic resonance imaging, and subsequently released into the aquatic environment. We investigated the consequences of sea urchin embryo exposure to sublethal Gd concentrations, comparing the effects on the development of four phylogenetically and geographically distant species: two Mediterranean species, Paracentrotus lividus and Arbacia lixula, and two species living in the East coast of Australia, Heliocidaris tuberculata and Centrostephanus rodgersii. Measures of the Gd and Ca content inside embryos by ICP-MS showed a time- and dose-dependent Gd increase, in parallel with a reduction of the Ca amount, suggesting that Gd is able to compete with Ca for binding to the Ca channels. In all the four species, we observed a general delay of embryo development at 24h post-fertilization, and a strong inhibition of skeleton growth at 48h, with species-specific threshold levels of sensitivity. Further experiments were carried out on P. lividus embryos. Removal of Gd after 24h caused partial recovery of embryo development 48h post fertilization. We detected an increase of the LC3 autophagic marker at 24 and 48h, while confocal microscopy studies confirmed the increased number of autophagosomes and autophagolysosomes. In contrast, immunofluorescence studies showed no apoptotic induction. RT-PCR gene expression analysis showed the misregulation of several genes implicated both in the skeletogenic and the left-right axis specification networks, including: transcription factors (Alx-1, Nodal), signaling molecules (univin, VEGF, VEGF-R, FGF) and skeletal matrix proteins (p16, p19 and msp130). Taken together, the results pose serious questions on the hazard of Gd in the marine environment and indicate that Gd is able to affect three different levels of the stress response in sea urchin embryos: morphogenesis, survival strategies such as autophagy, and gene expression
    Studies of congenital malformations and their etiology in wild animals are a powerful tool when considered in a holistic/overall evaluation of the “one health status”. Reptiles, according to their habitat and biological features, can be... more
    Studies of congenital malformations and their etiology in wild animals are a powerful tool when considered in a holistic/overall evaluation of the “one health status”. Reptiles, according to their habitat and biological features, can be promising predictors of environmental contamination. However, research in this area remains scarce and dispersed. The purpose of this review is to compile some documentation that describes or discusses the teratogenic effects of pesticides on reptiles. Further research in this area is urgently needed to implement concrete measures to improve ecosystem health and stop the present decline of reptile populations.
    The teratogenic effects of thermal stress were studied in the oviparous Italian wall lizard Podarcis sicula. To this purpose, the eggs were exposed to continuous or temporary cold (15°C) or warm (30°C) stresses and the effects were... more
    The teratogenic effects of thermal stress were studied in the oviparous Italian wall lizard Podarcis sicula. To this purpose, the eggs were exposed to continuous or temporary cold (15°C) or warm (30°C) stresses and the effects were analysed at the cytological and molecular levels. The results demonstrated the lethality of the continuous regimes and of the warm temporary regime, no matter if given at early (5 days) or late (15 days) stages of development. Temporary cold stress also resulted in lethality, but only if given in the early stage; later, in fact, it resulted in an abnormal development, with marked alterations in the encephalic vesicles, in the eyes and the trunk organs. By in situ hybridization, it was demonstrated that these alterations were often correlated with changes in HSP70 expression. In conclusion, our data indicate that Podarcis embryos have a limited potential to tolerate thermal changes, especially warm ones. The average predicted temperature increase of 2-4°C in the next few decades could therefore represent a real threat for lizard populations living in temperate areas.
    The present report is an attempt to investigate the influence of intraperitoneal and dietary cadmium exposure on the distribution of cadmium accumulation and induction of metallothionein gene expression in different tissues of the lizard... more
    The present report is an attempt to investigate the influence of intraperitoneal and dietary cadmium exposure on the distribution of cadmium accumulation and induction of metallothionein gene expression in different tissues of the lizard Podarcis sicula. Cadmium accumulation in liver, kidney, ovary, brain and intestine was measured by atomic absorption spectrometry. Metallothionein gene induction was determined by dot blot analyses on the total RNA extracted from the same organs. Our data indicate that cadmium exposure results in significant cadmium uptake, but the patterns of this uptake varies with organ and exposure route. After a single intraperitoneal treatment, concentrations of cadmium and metallothionein transcript are positively correlated in kidney, liver and ovary. Following a dietary cadmium treatment, a positive correlation between the increase of metallothionein mRNA and cadmium accumulation is found in intestine, ovary and kidney, while no correlation is present in liver and brain.
    Given their strong site fidelity and low mobility, lizards have been identified as potential model species for terrestrial vertebrate ecotoxicology since they can provide useful information about land-based pollution. Lizards can be... more
    Given their strong site fidelity and low mobility, lizards have been identified as potential model species for terrestrial vertebrate ecotoxicology since they can provide useful information about land-based pollution. Lizards can be directly exposed to fertilizers, pesticides and other chemical substances used in agriculture and livestock breeding through various routes: ingestion of soil and contaminated food, dermal exposure, inhalation, maternal transfer to eggs, and absorption by eggs of contaminants from environments. The advantage of using Podarcis sicula as a bioindicator of estrogen pollution is that its reproductive cycle is well known, both in males and females. Males, in particular, are excellent sentinels since they are able to synthesize vitellogenin (VTG) when exposed to an estrogenic environment; hence, VTG is commonly used as a biomarker of pollution from estrogenic compounds, mainly in aquatic or semi-aquatic species. In this chapter, we present data collected using P. sicula as an experimental model for monitoring soil health status in both intensive and organic farming, as well as for the study of damage caused at tissutal and cellular levels following environmental contamination by estrogenic compounds.
    Soil contaminants (herbicides, pesticides, and heavy metals) are among the main causes of change in terrestrial ecosystems. These substances lead to a general loss of biodiversity, both of flora and fauna and being able to biomagnify and... more
    Soil contaminants (herbicides, pesticides, and heavy metals) are among the main causes of change in terrestrial ecosystems. These substances lead to a general loss of biodiversity, both of flora and fauna and being able to biomagnify and pass through the food chain, they can endanger the survival of terrestrial vertebrates at the top of this chain. This review analyzes the risks associated with exposure to glyphosate, the active principle of many herbicide products, for the reproductive health of the field lizard (Podarcis siculus) potentially exposed to the substance in its natural habitat; therefore, introducing it as a possible model organism. Data demonstrate that glyphosate is toxic for this animal, affecting the health of the reproductive organs, both in males and females, and of the liver, the main detoxifying organ and closely involved in the female reproductive process. Sharing structural and functional characteristics of these organs with many other vertebrates, the inform...
    Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide involved in multiple functions, including vertebrate reproduction. Recently, we reported the presence of PACAP in the testis of Italian wall lizard Podarcis sicula... more
    Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide involved in multiple functions, including vertebrate reproduction. Recently, we reported the presence of PACAP in the testis of Italian wall lizard Podarcis sicula during reproductive period (May-June). Herein we investigated the PACAP mRNA expression and the localization of PACAP/PACAP receptor system, in the other periods of the Podarcis reproductive cycle, namely in summer stasis, early autumnal resumption, mid-autumnal resumption, winter stasis, and spring resumption. Using biomolecular and immunohistochemical investigations, we demonstrated that PACAP mRNA was widely expressed in all germ and somatic cells; in summer stasis (July-August) and early autumnal resumption (September) in particular, the mRNA was always found in Sertoli cells while was transiently expressed in germ and in Leydig cells. Differently from the mRNA, the protein was always present in germ and somatic cells independently from the reproductive cycle phase. As PACAP, the PAC1 receptor was always present in the testis, except for the summer stasis (July-August) and the early autumnal resumption (September), when PACAP was lacking in germ and somatic cells (Leydig and Sertoli cells). The present results strongly suggest that PACAP/PAC1 receptor system is widely represented during the reproductive cycle of male lizard. The possible involvement of PACAP/PACAP receptor system in the control of spermatogenesis is discussed.
    Glyphosate (Gly) is a broad-spectrum herbicide widely used thanks to its high efficiency and low toxicity. However, evidence exists of its toxic effects on non-target organisms. Among these, the animals inhabiting agricultural fields are... more
    Glyphosate (Gly) is a broad-spectrum herbicide widely used thanks to its high efficiency and low toxicity. However, evidence exists of its toxic effects on non-target organisms. Among these, the animals inhabiting agricultural fields are particularly threatened. Recent studies demonstrated that exposure to Gly markedly affected the morphophysiology of the liver and testis of the Italian field lizard Podarcis siculus. The present study aimed to investigate the effects of the herbicide on the female reproductive system of this lizard in order to have a full picture of Gly-induced reproductive impairment. The animals were exposed to 0.05 and 0.5 μg/kg of pure Gly by gavage for 3 weeks. The results demonstrated that Gly, at both doses tested, profoundly interfered with ovarian function. It induced germ cells’ recruitment and altered follicular anatomy by anticipating apoptotic regression of the pyriform cells. It also induced thecal fibrosis and affected oocyte cytoplasm and zona pelluc...
    doi: 10.3389/fncel.2014.00212 Haptoglobin increases with age in rat hippocampus and modulates Apolipoprotein E mediated cholesterol trafficking in neuroblastoma cell lines

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