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Expression of caspase‐3 in brains from paediatric patients with HIV‐1 encephalitis
Author(s) -
H. J. James,
Leroy R. Sharer,
Q. Zhang,
H. G. Wang,
Leon G. Epstein,
John C. Reed,
Harris A. Gelbard
Publication year - 1999
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.1999.00195.x
Subject(s) - microglia , encephalopathy , encephalitis , tunel assay , apoptosis , pathology , biology , downregulation and upregulation , immunology , caspase 3 , medicine , virology , virus , programmed cell death , inflammation , immunohistochemistry , gene , biochemistry
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.