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)

During Plasmodium falciparum infection leading to cerebral malaria, cytokine production and cytoadherence of parasitized erythrocytes (PRBCs) to postcapillary venules are involved. We demonstrate that PRBC adhesion induces apoptosis in human endothelial cells (HLECs). PRBC adhesion modulated HLEC gene expression in tumor necrosis factor-alpha superfamily genes (Fas, Fas L, and DR-6) and apoptosis-related genes (Bad, Bax, caspase-3,SARP 2, DFF45/ICAD, IFN-gamma receptor 2, Bcl-w, Bik, and iNOS). Apoptosis was confirmed by (1) morphological modifications by electron microscopy, (2) annexin V binding, (3) DNA degradation, by measuring intracytoplasmic nucleosomes, and (4) caspase activity. The apoptotic stimulus was physical contact between HLECs and PRBCs and not parasite-secreted molecules. In addition, it was found that cytoplasmic (caspase 8) and mitochondrial (caspase 9) pathways were involved in this process. These data not only describe the direct apoptotic effect of PRBC adhesion on endothelial cells but also provide new useful tools that allow an evaluation of potential pharmaceuticals.
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PMID:Plasmodium falciparum--infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. 1269 8

Cerebral malaria is a serious complication of Plasmodium falciparum infection. We have investigated the role of perforin in the pathogenesis of cerebral malaria in a murine model (Plasmodium berghei ANKA (PbA) infection). C57BL/6 mice demonstrated the typical neuropathological symptoms of experimental cerebral malaria infection from day 5p.i. and became moribund on day 6p.i. This pathology was not seen in PbA-infected, perforin-deficient (pfp-/-) mice. From days 5-6p.i. onwards there was a significant increase in mRNA for granzyme B and CD8, but not CD4, in brain tissue from PbA-infected C57BL/6 and pfp-/- mouse brains. Perforin mRNA was strongly increased in the brains of PbA-infected C57BL/6 mice on day 6p.i. Immunohistochemistry revealed increased perforin staining and elevated numbers of CD8(+) cells within the cerebral microvessels in PbA-infected C57BL/6 at days 5 and 6p.i. compared with uninfected animals. At day 6p.i., there were TUNEL-positive cells and activated caspase-3 positive cells of endothelial morphology in the CNS of PbA-infected C57BL/6 mice. The TUNEL-positive cells were greatly reduced in pfp-/- mice. These results suggest that CD8(+)T lymphocytes induce apoptosis of endothelial cells via a perforin-dependent process, contributing to the fatal pathogenic process in murine cerebral malaria.
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PMID:Perforin mediated apoptosis of cerebral microvascular endothelial cells during experimental cerebral malaria. 1650 Jun 56