Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify the mechanisms underlying capacitation, we undertook a high-resolution differential proteomic analysis of pig sperm cells. Two-dimensional gel electrophoresis and subsequent MALDI-TOF mass spectrometry analyses led to identification of 56 differentially expressed proteins. After induction of capacitation in vitro, the well-established markers of the capacitation (lactadherin P47, acrosomal protein SP-10 precursor, prohibitin, proteasomes, DJ-1 protein and arylsulfatase-A) and TCA cycle proteins (isocitrate dehydrogenase, malate dehydrogenase and pyruvate dehydrogenase) were identified. During induction, cytochrome c expression via the p53 pathway increased, however apoptotic executors, such as caspase-3, decreased significantly. Therefore, we tested the hypothesis that cytochrome c upregulation in spermatozoa is capable of activating tyrosine phosphorylation for capacitation, rather than apoptosis. Exposure of sperm cells to soluble Na2CrO4 [Cr (VI)], which induces cytochrome c upregulation, caused a dose- and time-dependent increase in tyrosine phosphorylation of sperm proteins in non-capacitating medium. In contrast, supplementation of cyclosporin A, which blocks cytochrome c upregulation, inhibited tyrosine phosphorylation of sperm proteins. Furthermore, spermatozoa in capacitation medium or non-capacitation media supplemented with soluble Cr (VI) showed similar levels of capacitation. These findings indicate that differential expression of many of these proteins has previously been unrecognized in sperm cells incubated in capacitation medium also suggest that a gradual increase of cytochrome c during incubation to induce capacitation determines sperm cell fate, i.e., apoptosis or further development for fertilization.
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PMID:Cytochrome c upregulation during capacitation and spontaneous acrosome reaction determines the fate of pig sperm cells: linking proteome analysis. 1809 29

Hydroperoxides are major products of the reactions of radicals and singlet oxygen with amino acids, peptides, and proteins. These species can generate radicals in the presence of metal ions and oxidize thiols via nonradical reactions, but the effects of these materials on cells are poorly understood. In this study the exposure of murine macrophage-like cells to preformed peptide or protein hydroperoxides is shown to result in hydroperoxide consumption and cellular thiol oxidation; these effects precede loss of cell viability. N-acetyltryptophan methyl ester hydroperoxides, but not the decomposed species, decreased total cellular thiols and GSH, with the latter occurring more rapidly. Time-dependent inhibition of lysosomal cathepsins B and L was also observed, together with diminished caspase 3/7 activity. A number of other cytosolic thiol- and non-thiol-dependent enzymes were not affected significantly. Hydroperoxides formed on BSA did not deplete total thiols or GSH within cells, although such reactions are rapid in model systems. In contrast, selective inhibition of cathepsins B and L (but not cathepsin D or arylsulfatase) of the endosomal-lysosomal system was detected, consistent with localization within these compartments. Decomposed BSA hydroperoxides did not induce these effects, indicating a requirement for the hydroperoxide group. The differences between these hydroperoxides are ascribed to their mechanisms of penetration into cells. Overall these studies provide valuable data on the initial cellular events arising from exposure to exogenous protein and amino acid peroxides and indicate that cellular thiols are a major target. This selective oxidation may modulate cellular redox balance and subsequent cell behavior.
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PMID:Cellular effects of peptide and protein hydroperoxides. 2010 44