Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis

H. J. James, L. R. Sharer, Q. Zhang, H. G. Wang, L. G. Epstein, J. C. Reed, H. A. Gelbard

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Apoptosis of neurones, macrophages, and microglia occurs in the brains of paediatric patients with human immunodeficiency virus (HIV) type 1 encephalitis, which is often associated with pre-mortem neurological disease (progressive encephalopathy). We have previously reported that TUNEL-positive neurones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic gene product Bax, in marked contrast to brain-resident macrophages and microglia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalopathy, as well as macrophages and microglia, but not astrocytes, overexpress caspase-3, a pro-apoptotic enzyme that is proteolytically activated downstream of Bax-Bcl-2 dysregulation. Co-localization of neuronal cytoplasmic caspase-3 and nuclear TUNEL staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 encephalitis and progressive encephalopathy. These findings suggest that vulnerable neurones in brain tissue from patients with HIV virus type 1 encephalitis and progressive encephalopathy undergo apoptosis by a mechanism that involves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl-2 dysregulation. Furthermore, caspase-3 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.

Original languageEnglish (US)
Pages (from-to)380-386
Number of pages7
JournalNeuropathology and Applied Neurobiology
Volume25
Issue number5
DOIs
StatePublished - Nov 3 1999

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

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