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Objective and Design: We have investigated whether transforming growth factor &#352 (TGF-&#352) influences the expression of inducible nitric oxide synthase... more
Objective and Design: We have investigated whether transforming growth factor &#352 (TGF-&#352) influences the expression of inducible nitric oxide synthase (iNOS).¶Material: Rat renal mesangial cells exposed to the inflammatory cytokine interleukin 1&#35 (IL-1&#35).¶Results: Addition of TGF-&#352 dose-dependently suppresses IL-1&#35-induced nitrite formation. Western and Northern blot analyses of mesangial cell extracts reveal that the inhibition of IL-1&#35-induced nitrite formation by TGF-&#352
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The activity of free extracellular dextranase inhibitor was determined in strains of Streptococcus sobrinus which were grown in a chemostat under a variety of defined conditions. Maximum release of dextranase inhibitor occurred at low... more
The activity of free extracellular dextranase inhibitor was determined in strains of Streptococcus sobrinus which were grown in a chemostat under a variety of defined conditions. Maximum release of dextranase inhibitor occurred at low growth rate in glucose-limited medium at pH 6.5. Free inhibitor could not be detected when the strains were grown at high growth rate or in batch culture.
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An Escherichia coli mutant lacking HSP70 function, delta dnaK52, is unable to grow at both high and low temperatures and, at intermediate temperature (30 degrees C), displays defects in major cellular processes such as cell division,... more
An Escherichia coli mutant lacking HSP70 function, delta dnaK52, is unable to grow at both high and low temperatures and, at intermediate temperature (30 degrees C), displays defects in major cellular processes such as cell division, chromosome segregation and regulation of heat shock gene expression that lead to poor growth and genetic instability of the cells. In an effort to understand the roles of molecular chaperones such as DnaK in cellular metabolism, we analyzed secondary mutations (sid) that suppress the growth defects of delta dnaK52 mutants at 30 degrees C and also permit growth at low temperature. Of the five suppressors we analyzed, four were of the sidB class and mapped within rpoH, which encodes the heat shock specific sigma subunit (sigma 32) of RNA polymerase. The sidB mutations affected four different regions of the sigma 32 protein and, in one case, resulted in a several fold reduction in the cellular concentration of sigma 32. Presence of any of the sidB mutations in delta dnaK52 mutants as well as in dnaK+ cells caused down-regulation of heat shock gene expression at 30 degrees C and decreased induction of the heat shock response after shift to 43.5 degrees C. These findings suggest that the physiologically most significant function of DnaK in the metabolism of unstressed cells is its function in heat shock gene regulation.
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We have investigated whether transforming growth factor beta 2 (TGF-beta 2) influences the expression of inducible nitric oxide synthase (iNOS). Rat renal mesangial cells exposed to the inflammatory cytokine interleukin 1 beta (IL-1... more
We have investigated whether transforming growth factor beta 2 (TGF-beta 2) influences the expression of inducible nitric oxide synthase (iNOS). Rat renal mesangial cells exposed to the inflammatory cytokine interleukin 1 beta (IL-1 beta). Addition of TGF-beta 2 dose-dependently suppresses IL-1 beta-induced nitrite formation. Western and Northern blot analyses of mesangial cell extracts reveal that the inhibition of IL-1 beta-induced nitrite formation by TGF-beta 2 is due to decreased iNOS protein and iNOS mRNA steady state levels. Reduction of iNOS mRNA levels is due to decreased transcriptional activity of the iNOS gene under the action of TGF-beta 2 as shown by nuclear run on experiments. TGF-beta 2 is a potent inhibitor of iNOS expression acting by reducing the transcriptional activity of the iNOS gene.
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Comparative gene expression studies are often limited by low availability of tissue and poor quality of extractable mRNA. Collective PCR amplification of minute quantities of mRNA has great potential for overcoming these limitations.... more
Comparative gene expression studies are often limited by low availability of tissue and poor quality of extractable mRNA. Collective PCR amplification of minute quantities of mRNA has great potential for overcoming these limitations. However, there remains significant concern about the effects of amplification on the absolute and relative abundance of individual mRNAs that could complicate subsequent gene expression studies. To address this problem, we systematically compared the relative abundance of many specific mRNAs from complex cDNA preparations (from tissue and cultured cells) both before and after amplification by PCR. Our results demonstrated that, as expected, the absolute abundance of different mRNAs in a cDNA library is altered in an unpredictable manner by PCR amplification. However, we found that the concentration ratios of specific mRNAs among different cDNA preparations were routinely well conserved after PCR amplification. Thus, for the purpose of comparative expres...
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Expression of group II phospholipase A2 (PLA2; EC 3.1.1.4) in rat renal mesangial cells is triggered in response to two principal classes of activating signals. These two groups of activators comprise inflammatory cytokines such as... more
Expression of group II phospholipase A2 (PLA2; EC 3.1.1.4) in rat renal mesangial cells is triggered in response to two principal classes of activating signals. These two groups of activators comprise inflammatory cytokines such as interleukin 1beta (IL-1beta) or tumor necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP) such as forskolin, an activator of adenylate cyclase. Treatment of mesangial cells with IL-1beta or forskolin for 24 h induces group II PLA2 activity secreted into cell culture supernatants by about 15-fold and 11-fold, respectively. Platelet-derived growth factor (PDGF)-BB potently inhibits secretion of IL-1beta- and forskolin-induced group II PLA2 activity. By Western and Northern blot analyses, we demonstrate that this is due to a reduction of PLA2 protein levels and the corresponding PLA2 mRNA steady-state levels. Basic fibroblast growth factor (bFGF) virtually does not inhibit IL-1beta-stimulated group II PLA2 activity, but markedl...
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Inducible nitric oxide synthase (iNOS; EC 1.14.13.39) is expressed in rat glomerular mesangial cells upon exposure to the inflammatory cytokine interleukin 1 beta (IL-1 beta). We have reported that nanomolar concentrations of... more
Inducible nitric oxide synthase (iNOS; EC 1.14.13.39) is expressed in rat glomerular mesangial cells upon exposure to the inflammatory cytokine interleukin 1 beta (IL-1 beta). We have reported that nanomolar concentrations of dexamethasone suppress IL-1 beta-induced iNOS protein expression and production of nitrite, the stable end product of NO formation, without affecting IL-1 beta-triggered increase in iNOS mRNA levels. We now have studied the mechanisms by which dexamethasone suppresses IL-1 beta-stimulated iNOS expression in mesangial cells. Surprisingly, nuclear run-on transcription experiments demonstrate that dexamethasone markedly attenuates IL-1 beta-induced iNOS gene transcription. However, this is counteracted by a prolongation of the half-life of iNOS mRNA from 1 h to 2.5 h by dexamethasone. Moreover, dexamethasone drastically reduces the amount of iNOS protein by reduction of iNOS mRNA translation and increased degradation of iNOS protein. These results indicate that glucocorticoids act at multiple levels to regulate iNOS expression, thus providing important insights into the treatment of inflammatory diseases.
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Research Interests: Genetics, Brazil, Cell Adhesion, Dermatology, Adolescent, and 20 moreHumans, Child, Basement Membrane, Haplotypes, Chronic Disease, Female, Male, Young Adult, Risk factors, Epidermis, Clinical Sciences, Family Health, Adult, Single Nucleotide Polymorphism, Genetic variation, Vitiligo, Risk Factors, INVESTIGATIVE, Confidence Interval, and Case Control Studies
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In recent years, NO, a gas previously considered a potentially toxic chemical, has become established as a diffusible universal messenger mediating cell-cell communication throughout the body. In mammals, NO is a recognized mediator of... more
In recent years, NO, a gas previously considered a potentially toxic chemical, has become established as a diffusible universal messenger mediating cell-cell communication throughout the body. In mammals, NO is a recognized mediator of blood vessel relaxation that helps to maintain blood pressure. In the central nervous system NO acts as a non-conventional neurotransmitter and participates in the establishment of long-term plasticity required for memory formation. In addition, NO is responsible for some parts of the host response to sepsis and inflammation and contributes to certain disease states. A number of strategies have emerged with regard to a pharmacological control of pathological NO overproductions. This review will discuss these novel therapeutic approaches that may provide new means for clinical medicine.