PMID- 16822952
OWN - NLM
STAT- MEDLINE
DCOM- 20061124
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 291
IP  - 5
DP  - 2006 Nov
TI  - HO-2 provides endogenous protection against oxidative stress and apoptosis caused 
      by TNF-alpha in cerebral vascular endothelial cells.
PG  - C897-908
AB  - Tumor necrosis factor-alpha (TNF-alpha) causes oxidative stress and apoptosis in 
      a variety of cell types. Heme oxygenase (HO) degrades heme to bilirubin, an 
      antioxidant, and carbon monoxide (CO), a cell cycle modulator, and a vasodilator. 
      Newborn pig cerebral microvascular endothelial cells (CMVEC) highly express 
      constitutive HO-2. We investigated the role of HO-2 in protection against 
      TNF-alpha-induced apoptosis in cerebral vascular endothelium. In CMVEC from mice 
      and newborn pigs, 15 ng/ml TNF-alpha alone, or with 10 microg/ml cycloheximide 
      (CHX) caused apoptosis detected by nuclear translocation of p65 NF-kappaB, 
      caspase-3 activation, DNA fragmentation, cell-cell contact destabilization, and 
      cell detachment. TNF-alpha did not induce HO-1 expression in CMVEC. CMVEC from 
      HO-2 knockout mice showed greater sensitivity to apoptosis caused by serum 
      deprivation and TNF-alpha than did wild-type mice. TNF-alpha increased reactive 
      oxygen species generation, including hydrogen peroxide and superoxide radicals, 
      as detected by dihydrorhodamine-123 and dihydroethidium. The TNF-alpha response 
      was inhibited by superoxide dismutase and catalase suggesting apoptosis is 
      oxidative stress related. Inhibition of endogenous HO-2 in newborn pig CMVEC 
      increased oxidative stress and exaggerated apoptosis caused by serum deprivation 
      and TNF-alpha. In HO-1-overexpressing CMVEC (HO-1 selective induction by cobalt 
      portophyrin), TNF-alpha did not cause apoptosis. A CO-releasing compound, 
      CORM-A1, and bilirubin blocked TNF-alpha-induced reactive oxygen species 
      accumulation and apoptosis consistent with the antioxidant and antiapoptotic 
      roles of the end products of HO activity. We conclude that HO-2 is critical for 
      protection of cerebrovascular endothelium against apoptotic changes induced by 
      oxidative stress and cytokine-mediated inflammation.
FAU - Basuroy, Shyamali
AU  - Basuroy S
AD  - Dept. of Physiology, University of Tennessee Health Science Center, Memphis, TN 
      38163, USA. sbasuroy@physio1.utmem.edu
FAU - Bhattacharya, Sujoy
AU  - Bhattacharya S
FAU - Tcheranova, Dilyara
AU  - Tcheranova D
FAU - Qu, Yan
AU  - Qu Y
FAU - Regan, Raymond F
AU  - Regan RF
FAU - Leffler, Charles W
AU  - Leffler CW
FAU - Parfenova, Helena
AU  - Parfenova H
LA  - eng
GR  - R01 HL034059/HL/NHLBI NIH HHS/United States
GR  - R01 NS046385/NS/NINDS NIH HHS/United States
GR  - R01 NS063936/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060705
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Isoenzymes)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (heme oxygenase-2)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/*drug effects
MH  - Bilirubin/pharmacology
MH  - Brain/*cytology/*drug effects
MH  - Carbon Monoxide/pharmacology
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/enzymology/metabolism/pathology
MH  - Gene Expression/drug effects
MH  - Heme Oxygenase (Decyclizing)/antagonists & inhibitors/*metabolism
MH  - Heme Oxygenase-1/metabolism
MH  - Isoenzymes/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Protein Transport/drug effects
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Swine
MH  - Tumor Necrosis Factor-alpha/*toxicity
MH  - Up-Regulation/drug effects
EDAT- 2006/07/11 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/07/11 09:00
PHST- 2006/07/11 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/07/11 09:00 [entrez]
AID - 00032.2006 [pii]
AID - 10.1152/ajpcell.00032.2006 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2006 Nov;291(5):C897-908. doi: 
      10.1152/ajpcell.00032.2006. Epub 2006 Jul 5.