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Sridar Chittur

Publications and source records attributed to Sridar Chittur.

5 recordsLinked to original sources
PubMed2006

Cerebellar granule cell death induced by aluminum.

Using flow cytometry of acutely isolated cerebellar granule cell neurons, we have determined the effects of Al (III) on viability, membrane potential, intracellular calcium concentration and generation of reactive oxygen species (ROS). Al (III) killed granule cells in a time- and concentration-dependent fashion when monitored by use of the DNA-binding dye, propidium iodide. The threshold concentration was about 50 micromolar, and cell death at 100 micromolar was apparent after 30 min exposure and increased over time. Cell death was accompanied by cell swelling and a decrease in membrane potential, and was not dependent on external calcium concentration. While exposure to Al (III) was accompanied by an increase in ROS and an elevation of intracellular calcium concentration, calcium chelators and ROS scavengers did not reduce cell death. The action of Al (III) was not accompanied by activation of caspase-3 or an increase in annexin-V binding, both indicators of apoptosis. In the presence of intracellular O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid (BAPTA) and absence of extracellular calcium there was still a fluo-3 signal, which likely reflects an accumulation of intracellular Al (III). These observations suggest that the cell death is subsequent to intracellular accumulation of Al (III) and subsequent perturbation of cellular metabolism.

Aluminum↗
PubMed2005

NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release.

Muscle wasting (cachexia) is a consequence of chronic diseases, such as cancer, and is associated with degradation of muscle proteins such as MyoD. The cytokines tumor necrosis factor alpha and gamma interferon induce muscle degeneration by activating the transcription factor NF-kappaB and its target genes. Here, we show that a downstream target of NF-kappaB is the nitric oxide (NO) synthase gene (iNos) and suggest that NO production stimulates MyoD mRNA loss. In fact, although cytokine treatment of iNos(-/-) mice activated NF-kappaB, it did not trigger MyoD mRNA degeneration, demonstrating that NF-kappaB-mediated muscle wasting requires an active iNOS-NO pathway. The induced expression of iNOS by cytokines relies on both transcriptional activation via NF-kappaB and increased mRNA stability via the RNA-binding protein HuR. Moreover, we show that HuR regulates iNOS expression in an AMP-activated protein kinase (AMPK)-dependent manner. Furthermore, AMPK activation results in HuR nuclear sequestration, inhibition of iNOS synthesis, and reduction in cytokine-induced MyoD loss. These results define iNOS and HuR as critical players in cytokine-induced cachexia, establishing them as potential therapeutic targets.

Animals↗
PubMed2005

Genomic expression patterns of cardiac tissues from dogs with dilated cardiomyopathy.

OBJECTIVE: To evaluate global genome expression patterns of left ventricular tissues from dogs with dilated cardiomyopathy (DCM). SAMPLE POPULATION: Tissues obtained from the left ventricle of 2 Doberman Pinschers with end-stage DCM and 5 healthy control dogs. PROCEDURE: Transcriptional activities of 23,851 canine DNA sequences were determined by use of an oligonucleotide microarray. Genome expression patterns of DCM tissue were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and comparing it with gene expression for tissues from 5 healthy control dogs. RESULTS: 478 transcripts were differentially expressed (> or = 2.5-fold change). In DCM tissue, expression of 173 transcripts was upregulated and expression of 305 transcripts was downregulated, compared with expression for control tissues. Of the 478 transcripts, 167 genes could be specifically identified. These genes were grouped into 1 of 8 categories on the basis of their primary physiologic function. Grouping revealed that pathways involving cellular energy production, signaling and communication, and cell structure were generally downregulated, whereas pathways involving cellular defense and stress responses were upregulated. Many previously unreported genes that may contribute to the pathophysiologic aspects of heart disease were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of global expression patterns provides a molecular portrait of heart failure, yields insights into the pathophysiologic aspects of DCM, and identifies intriguing genes and pathways for further study.

Animals↗
PubMed2004

Rodent lymphocytes express functionally active glutamate receptors.

RT-PCR demonstrated that ionotropic (iGluR NR1) and metabotropic (mGluR Group III) glutamate receptors are expressed in rodent lymphocytes. Flow cytometry showed that activation of iGluR NR1 by N-methyl-D-aspartate (NMDA) increased intracellular free calcium and reactive oxygen species (ROS) levels and activated caspase-3. The latter effect was attenuated by the NMDA antagonist, 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), by the antioxidant N-acetylcysteine and by cyclosporin A. Treatment with L-2-amino-4-phosphonobutyric acid (L-AP4), an mGluR Group III agonist, increased lymphocyte ROS levels but to a lower extent than did NMDA. Activation of lymphocytes with both NMDA and L-AP4 caused a synergistic increase in ROS levels and induced necrotic cellular death without elevating the caspase-3 activation observed in the presence of NMDA alone. These results show that lymphocyte iGluR NR1 and mGluR Group III receptors may be involved in controlling rodent lymphocyte functions and longevity as they regulate events in cell proliferation, maturation, and death.

Aminobutyrates↗