Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis.
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.
James
H J
HJ
Department of Neurology (Child Neurology Division), The University of Rochester Medical Center, NY 14642, USA.
Sharer
L R
LR
Zhang
Q
Q
Wang
H G
HG
Epstein
L G
LG
Reed
J C
JC
Gelbard
H A
HA
D015526:AIDS Dementia Complex / Q000201:enzymology / Q000235:genetics; D000293:Adolescent; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000201:enzymology; D053938:DNA Fragmentation; D004660:Encephalitis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000201:enzymology* / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D017628:Microglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology
C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases