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

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

Research output: Contribution to journalArticle

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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

Fingerprint

Brain Diseases
Encephalitis
Caspase 3
HIV-1
Pediatrics
Neurons
Microglia
Brain
Macrophages
In Situ Nick-End Labeling
Up-Regulation
Encephalitis Viruses
Apoptosis
DNA Fragmentation
Genetic Markers
Astrocytes
HIV
Staining and Labeling
Enzymes
Genes

All Science Journal Classification (ASJC) codes

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

Cite this

James, H. J. ; Sharer, L. R. ; Zhang, Q. ; Wang, Hong-Gang ; Epstein, L. G. ; Reed, J. C. ; Gelbard, H. A. / Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis. In: Neuropathology and Applied Neurobiology. 1999 ; Vol. 25, No. 5. pp. 380-386.
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Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis. / James, H. J.; Sharer, L. R.; Zhang, Q.; Wang, Hong-Gang; Epstein, L. G.; Reed, J. C.; Gelbard, H. A.

In: Neuropathology and Applied Neurobiology, Vol. 25, No. 5, 03.11.1999, p. 380-386.

Research output: Contribution to journalArticle

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