Effect of recombinant human activated protein C on apoptosis-related proteins.
The recombinant human activated protein C (rhAPC) has been reported to reduce mortality in patients with severe sepsis. An anti-apoptotic effect of rhAPC in sepsis is known, but the mechanism through which it acts on the apoptotic pathway is still unclear. Therefore, immunopositivity of the apoptosis-related proteins Bcl-2, an anti-apoptotic protein, c-myc, a proliferative protein, p-21 and p-53, two apoptotic proteins, was determined after rhAPC treatment in a mouse sepsis model. Sepsis was induced by Escherichia coli endotoxin injection. Increased neutrophil infiltration and immunoreactivity to p53 and p21 were observed in the group with sepsis and these immunoreactivities were decreased by rhAPC treatment. In the sepstic group; immunopositivity of Bcl-2 and c-myc was mild and moderate, respectively. In conclusion; p21- and p53-mediated apoptosis was increased in the sepsis model, and for the first time it has been shown that rhAPC decreases sepsis-induced apoptosis resulting from increased p21 and p53 proteins.
Department of Pulmonology, Celal Bayar University Medical School, Manisa, Turkey. aysins@hotmail.com
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Sakar
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Vatansever
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Sepit
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Ozbilgin
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Yorgancioglu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011486:Protein C / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; C489428:Myc protein, mouse; D011486:Protein C; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53