PMID- 10037731
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 10
DP  - 1999 Mar 5
TI  - 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic
      cell death.
PG  - 6397-404
AB  - To determine the contribution of 150-kDa oxygen-regulated protein (ORP150) to
      cellular processes underlying adaptation to hypoxia, a cell line stably
      transfected to overexpress ORP150 antisense RNA was created. In human embryonic
      kidney (HEK) cells stably overexpressing ORP150 antisense RNA, ORP150 antigen and
      transcripts were suppressed to low levels in normoxia and hypoxia, whereas
      wild-type cells showed induction of ORP150 with oxygen deprivation. Inhibition of
      ORP150 in antisense transfectants was selective, as hypoxia-mediated enhancement 
      of glucose-regulated protein (GRP) 78 and GRP94 was maintained. However,
      antisense ORP150 transfectants displayed reduced viability when subjected to
      hypoxia, compared with wild-type and sense-transfected HEK cells. In contrast,
      diminished levels of ORP150 had no effect on cytotoxicity induced by other
      stimuli, including oxygen-free radicals and sodium arsenate. Although cellular
      ATP content was similar in hypoxia, compared with ORP150 antisense transfectants 
      and wild-type HEK cells, suppression of ORP150 expression was associated with
      accelerated apoptosis. Hypoxia-mediated cell death in antisense HEK transfectants
      did not cause an increase in caspase activity or in cytoplasmic cytochrome c
      antigen. A well recognized inducer of apoptosis in HEK cells, staurosporine,
      caused increased caspase activity and cytoplasmic cytochrome c levels in both
      wild-type and antisense cells. These data indicate that ORP150 has an important
      cytoprotective role in hypoxia-induced cellular perturbation and that
      ORP150-associated inhibition of apoptosis may involve mechanisms distinct from
      those triggered by other apoptotic stimuli.
FAU - Ozawa, K
AU  - Ozawa K
AD  - Department of Anatomy and Neuroscience, Biomedical Research Center, Osaka
      University Medical School, 2-2 Yamada-oka, Suita City 565, Japan.
      ozawa@anat2.med.osaka-u.ac.jp
FAU - Kuwabara, K
AU  - Kuwabara K
FAU - Tamatani, M
AU  - Tamatani M
FAU - Takatsuji, K
AU  - Takatsuji K
FAU - Tsukamoto, Y
AU  - Tsukamoto Y
FAU - Kaneda, S
AU  - Kaneda S
FAU - Yanagi, H
AU  - Yanagi H
FAU - Stern, D M
AU  - Stern DM
FAU - Eguchi, Y
AU  - Eguchi Y
FAU - Tsujimoto, Y
AU  - Tsujimoto Y
FAU - Ogawa, S
AU  - Ogawa S
FAU - Tohyama, M
AU  - Tohyama M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Proteins)
RN  - 0 (RNA, Antisense)
RN  - 0 (oxygen-regulated proteins)
SB  - IM
MH  - Apoptosis/*genetics
MH  - *Cell Hypoxia
MH  - Cell Line
MH  - *Gene Expression Regulation
MH  - HSP70 Heat-Shock Proteins
MH  - Humans
MH  - Proteins/*genetics
MH  - RNA, Antisense
MH  - Transfection
EDAT- 1999/02/26 00:00
MHDA- 1999/02/26 00:01
CRDT- 1999/02/26 00:00
PHST- 1999/02/26 00:00 [pubmed]
PHST- 1999/02/26 00:01 [medline]
PHST- 1999/02/26 00:00 [entrez]
AID - 10.1074/jbc.274.10.6397 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Mar 5;274(10):6397-404. doi: 10.1074/jbc.274.10.6397.