PMID- 16127150
OWN - NLM
STAT- MEDLINE
DCOM- 20051107
LR  - 20211203
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 167
IP  - 3
DP  - 2005 Sep
TI  - Characterization of cell death pathways in human immunodeficiency 
      virus-associated encephalitis.
PG  - 695-704
AB  - Human immunodeficiency virus (HIV)-associated dementia is a neurodegenerative 
      syndrome characterized by cognitive decline, personality change, and motor 
      deficits. HIV-associated encephalitis (HAE), the neuropathology responsible for 
      HIV-associated dementia, involves the formation of multinucleated giant cells or 
      syncytia. In this article we describe the apoptotic pathways activated in the 
      brains of HAE-affected patients. Approximately 50% of multinuclear giant cells 
      exhibited apoptotic DNA fragmentation as detected by the terminal dUTP nick-end 
      labeling technique. In addition, the presence of syncytia in the frontal cortex 
      of approximately 35% of HAE patients correlated with the number of cells 
      expressing the HIV-1 protein p24. Histochemical and immunohistochemical analyses 
      revealed that HAE-associated syncytia underwent apoptosis through a mitochondrial 
      pathway previously delineated for HIV-1 envelope-elicited syncytia in vitro. We 
      observed over-expression of the mammalian target of rapamycin (mTOR), a kinase 
      that mediates activation of the pro-apoptotic transcription factor p53, and 
      p53-dependent up-regulation of two effectors of mitochondrial apoptosis, namely 
      the BH3-only proteins Puma and transglutaminase type 2 (TG2). Interestingly, 
      although mTOR activation and Puma induction were observed in dying syncytia and 
      neurons, IkB phosphorylation and TG2 up-regulation were only found in syncytia. 
      These findings provide substantial new information on the cell death mechanisms 
      that regulate HAE, suggesting an important pathogenetic role of syncytia in the 
      disease.
FAU - Nardacci, Roberta
AU  - Nardacci R
AD  - National Institute for Infectious Diseases, University of Rome, 00149 Rome, 
      Italy.
FAU - Antinori, Andrea
AU  - Antinori A
FAU - Larocca, Luigi Maria
AU  - Larocca LM
FAU - Arena, Vincenzo
AU  - Arena V
FAU - Amendola, Alessandra
AU  - Amendola A
FAU - Perfettini, Jean-Luc
AU  - Perfettini JL
FAU - Kroemer, Guido
AU  - Kroemer G
FAU - Piacentini, Mauro
AU  - Piacentini M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Acquired Immunodeficiency Syndrome
MH  - Adult
MH  - Apoptosis
MH  - Brain/pathology/physiopathology
MH  - Cell Death
MH  - Encephalitis/pathology/*physiopathology/*virology
MH  - Female
MH  - Giant Cells/metabolism/pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neurons/metabolism
MH  - Protein Kinases/metabolism
MH  - Severity of Illness Index
MH  - TOR Serine-Threonine Kinases
PMC - PMC1698734
EDAT- 2005/08/30 09:00
MHDA- 2005/11/08 09:00
PMCR- 2006/03/01
CRDT- 2005/08/30 09:00
PHST- 2005/08/30 09:00 [pubmed]
PHST- 2005/11/08 09:00 [medline]
PHST- 2005/08/30 09:00 [entrez]
PHST- 2006/03/01 00:00 [pmc-release]
AID - S0002-9440(10)62044-5 [pii]
AID - 10.1016/S0002-9440(10)62044-5 [doi]
PST - ppublish
SO  - Am J Pathol. 2005 Sep;167(3):695-704. doi: 10.1016/S0002-9440(10)62044-5.