Mitochondrial anomalies are associated with the induction of intrinsic cell death proteins-Bcl(2), Bax, cytochrome-c and p53 in mice brain during experimental fatal murine cerebral malaria.
The levels of apoptosis associated proteins Bcl(2), Bax, cytochrome-c and p53 was investigated in mice cerebral cortex and cerebellum, using an experimental model of fatal murine cerebral malaria (FMCM). Owing to the activation of events central to mitochondrial dysfunctions, we monitored the structural integrity of mitochondria in cerebral malaria (CM) infected brain tissue by transmission EM (TEM) studies. Western blot analysis revealed the induction of Bcl(2), Bax, cytochrome-c and p53 in both cortex and cerebellum. The TEM studies revealed extensive vacuolation and swelling of mitochondria in infected brain suggestive of a late stage of degeneration. Our results underscore the activation of an intrinsic cell death pathway as evinced by the induction of mitochondria associated apoptotic proteins Bcl(2), Bax and cytochrome-c and further envisages the induction of p53 as a possible continuation of the post receptor signaling events associated with tumor necrosis factor induction following inflammatory responses during CM. These findings may be crucial to mitochondrial dysfunctions underlying the pathology of FMCM.
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
Kota Arun
KA
Kumar
Phanithi Prakash
PP
Babu
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D003574:Cytochrome c Group / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D016779:Malaria, Cerebral / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism / Q000469:parasitology / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D003574:Cytochrome c Group; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein