PMID- 11490367
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20131121
IS  - 0039-6060 (Print)
IS  - 0039-6060 (Linking)
VI  - 130
IP  - 2
DP  - 2001 Aug
TI  - Nitric oxide mediates dendritic cell apoptosis by downregulating inhibitors of 
      apoptosis proteins and upregulating effector caspase activity.
PG  - 326-32
AB  - BACKGROUND: Dendritic cells (DCs) play a crucial role in the amplification of the 
      immune response by promoting antigen presentation, T-lymphocyte proliferation, 
      and proinflammatory cytokine and nitric oxide (NO) production. We have previously 
      shown that the exogenous NO donor, s-nitroso-N-acetyl-penicillamine, promotes DC 
      apoptosis by disrupting the mitochondrial membrane potential, which induces 
      cytochrome-C release and activates caspase 3. To further elucidate the signaling 
      pathway, we examined the expression of cellular inhibitors of apoptosis proteins 
      (cIAPs) and poly (ADP-ribose) polymerase cleavage (PARP), a terminal event in the 
      apoptotic cascade. METHODS: DC2.4 were exposed to 250 micromol/L 
      s-nitroso-N-acetyl-penicillamine for various intervals. Apoptosis and necrosis 
      were measured by terminal deoxynucleotidyl transferase nick-end labeling assay or 
      flow cytometry with Annexin V and propidium iodide. DC2.4 were cultured with the 
      pan-caspase inhibitor, ZVAD (100 micromol/L). cIAP, pro-caspases, and PARP 
      expression or activation was measured by Western blot. Caspase enzyme activity 
      was confirmed with the use of specific substrates. RESULTS: NO-induced DC 
      apoptosis correlated with the downregulation of cIAP expression. Caspase 3 and 6 
      were upregulated by SNAP and significantly inhibited by ZVAD. Maximal PARP 
      cleavage occurred at 8 hours and coincided with the downregulation of cIAP and 
      peak caspase 3 and near maximal caspase 6 activity. CONCLUSIONS: NO-induced DC 
      apoptosis is associated with the downregulation of cIAP expression, which 
      facilitates caspase cascade activation and subsequent PARP cleavage.
FAU - Stanford, A
AU  - Stanford A
AD  - Department of Surgery, Children's Hospital of Pittsburgh and the University of 
      Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
FAU - Chen, Y
AU  - Chen Y
FAU - Zhang, X R
AU  - Zhang XR
FAU - Hoffman, R
AU  - Hoffman R
FAU - Zamora, R
AU  - Zamora R
FAU - Ford, H R
AU  - Ford HR
LA  - eng
GR  - R01-AI-14032/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (S-nitro-N-acetylpenicillamine)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Casp6 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 6)
RN  - EC 3.4.22.- (Caspases)
RN  - GNN1DV99GX (Penicillamine)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - Animals
MH  - Apoptosis/*immunology
MH  - Bone Marrow Cells/cytology
MH  - Caspase 3
MH  - Caspase 6
MH  - Caspases/*metabolism
MH  - Cell Line, Transformed
MH  - Cell Survival/immunology
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - Dendritic Cells/*cytology/immunology/metabolism
MH  - Down-Regulation/immunology
MH  - Enzyme Activation/drug effects
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - Penicillamine/analogs & derivatives/pharmacology
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Up-Regulation/immunology
EDAT- 2001/08/08 10:00
MHDA- 2001/09/08 10:01
CRDT- 2001/08/08 10:00
PHST- 2001/08/08 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/08/08 10:00 [entrez]
AID - S0039-6060(01)77150-4 [pii]
AID - 10.1067/msy.2001.116411 [doi]
PST - ppublish
SO  - Surgery. 2001 Aug;130(2):326-32. doi: 10.1067/msy.2001.116411.