PMID- 10438538
OWN - NLM
STAT- MEDLINE
DCOM- 19990901
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 33
DP  - 1999 Aug 13
TI  - Selective activation of p38alpha and p38gamma by hypoxia. Role in regulation of
      cyclin D1 by hypoxia in PC12 cells.
PG  - 23570-6
AB  - Hypoxic/ischemic trauma is a primary factor in the pathology of a multitude of
      disease states. The effects of hypoxia on the stress- and mitogen-activated
      protein kinase signaling pathways were studied in PC12 cells. Exposure to
      moderate hypoxia (5% O(2)) progressively stimulated phosphorylation and
      activation of p38gamma in particular, and also p38alpha, two stress-activated
      protein kinases. In contrast, hypoxia had no effect on enzyme activity of
      p38beta, p38beta(2), p38delta, or on c-Jun N-terminal kinase, another
      stress-activated protein kinase. Prolonged hypoxia also induced phosphorylation
      and activation of p42/p44 mitogen-activated protein kinase, although this
      activation was modest compared with nerve growth factor- and ultraviolet
      light-induced activation. Hypoxia also dramatically down-regulated
      immunoreactivity of cyclin D1, a gene that is known to be regulated negatively by
      p38 at the level of gene expression (Lavoie, J. N., L'Allemain, G., Brunet, A.,
      Muller, R., and Pouyssegur, J. (1996) J. Biol. Chem. 271, 20608-20616). This
      effect was partially blocked by SB203580, an inhibitor of p38alpha but not
      p38gamma. Overexpression of a kinase-inactive form of p38gamma was also able to
      reverse in part the effect of hypoxia on cyclin D1 levels, suggesting that
      p38alpha and p38gamma converge to regulate cyclin D1 during hypoxia. These
      studies demonstrate that an extremely typical physiological stress (hypoxia)
      causes selective activation of specific p38 signaling elements; and they also
      identify a downstream target of these pathways.
FAU - Conrad, P W
AU  - Conrad PW
AD  - Department of Molecular and Cellular Physiology, College of Medicine, University 
      of Cincinnati, Cincinnati, Ohio 45267-0576, USA.
FAU - Rust, R T
AU  - Rust RT
FAU - Han, J
AU  - Han J
FAU - Millhorn, D E
AU  - Millhorn DE
FAU - Beitner-Johnson, D
AU  - Beitner-Johnson D
LA  - eng
GR  - HL07571/HL/NHLBI NIH HHS/United States
GR  - R01HL59945/HL/NHLBI NIH HHS/United States
GR  - R37HL33831/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Isoenzymes)
RN  - 0 (Transcription Factors)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - *Cell Hypoxia
MH  - Cyclin D1/metabolism
MH  - Enzyme Activation
MH  - Isoenzymes/*metabolism
MH  - *Mitogen-Activated Protein Kinases
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Rats
MH  - Transcription Factors/metabolism
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 1999/08/07 00:00
MHDA- 1999/08/07 00:01
CRDT- 1999/08/07 00:00
PHST- 1999/08/07 00:00 [pubmed]
PHST- 1999/08/07 00:01 [medline]
PHST- 1999/08/07 00:00 [entrez]
AID - 10.1074/jbc.274.33.23570 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 13;274(33):23570-6. doi: 10.1074/jbc.274.33.23570.