PMID- 12529177
OWN - NLM
STAT- MEDLINE
DCOM- 20030703
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 371
IP  - Pt 2
DP  - 2003 Apr 15
TI  - Osmotic regulation of insulin-induced mitogen-activated protein kinase 
      phosphatase (MKP-1) expression in H4IIE rat hepatoma cells.
PG  - 609-19
AB  - A contribution of intracellular dehydration to insulin resistance has been 
      established in human subjects and in different experimental systems. Here the 
      effect of hyperosmolarity (405 mosmol/l) on insulin-induced mitogen-activated 
      protein (MAP) kinase phosphatase (MKP)-1 expression was studied in H4IIE rat 
      hepatoma cells. Insulin induces robust MKP-1 expression which correlates with a 
      vanadate-sensitive decay of extracellular-signal-regulated kinase (Erk-1/Erk-2) 
      activity. Hyperosmolarity delays MKP-1 accumulation by insulin and this 
      corresponds to impaired MKP-1 synthesis, whereas MKP-1 degradation remains 
      unaffected by hyperosmolarity. Rapamycin, which inhibits signalling downstream 
      from the mammalian target of rapamycin (mTOR) and a peptide inhibiting protein 
      kinase C (PKC) zeta/lambda abolish insulin-induced MKP-1 protein but not mRNA 
      expression, suggesting the involvement of the p70 ribosomal S6 protein kinase 
      (p70S6-kinase) and/or the eukaryotic initiation factor 4E-binding proteins 
      (4E-BPs) as well as atypical PKCs in MKP-1 translation. Hyperosmolarity induces 
      sustained suppression of p70S6-kinase and 4E-BP1 hyperphosphorylation by insulin, 
      whereas insulin-induced tyrosine phosphorylation of the insulin receptor (IR) 
      beta subunit and the IR substrates IRS1 and IRS2, recruitment of the 
      phosphoinositide 3-kinase (PI 3-kinase) regulatory subunit p85 to the receptor 
      substrates as well as PI 3-kinase activation, and Ser-473 phosphorylation of 
      protein kinase B and Thr-410/403 phosphorylation of PKC zeta/lambda are largely 
      unaffected under hyperosmotic conditions. The hyperosmotic impairment of both, 
      MKP-1 expression and p70S6-kinase hyperphosphorylation by insulin is insensitive 
      to K(2)CrO(4), calyculin A and vanadate, and inhibition of the Erk-1/Erk-2 and 
      p38 pathways. The suppression of MKP-1 may further contribute to insulin 
      resistance under dehydrating conditions by allowing unbalanced MAP kinase 
      activation.
FAU - Lornejad-Schafer, Mohammad Reza
AU  - Lornejad-Schafer MR
AD  - Medizinische Einrichtungen der Heinrich-Heine Universitat, Klinik fur 
      Gastroenterologie, Hepatologie und Infektiologie, Moorenstrasse 5, D-40225 
      Dusseldorf, Germany.
FAU - Schafer, Christine
AU  - Schafer C
FAU - Graf, Dirk
AU  - Graf D
FAU - Haussinger, Dieter
AU  - Haussinger D
FAU - Schliess, Freimut
AU  - Schliess F
LA  - eng
PT  - Journal Article
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Insulin)
RN  - 0 (RNA, Messenger)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
RN  - EC 3.1.3.48 (DUSP1 protein, human)
RN  - EC 3.1.3.48 (Dual Specificity Phosphatase 1)
RN  - EC 3.1.3.48 (Dusp1 protein, rat)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular
MH  - *Cell Cycle Proteins
MH  - Dual Specificity Phosphatase 1
MH  - Enzyme Induction/drug effects
MH  - Gene Expression Regulation, Enzymologic
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Immediate-Early Proteins/biosynthesis/*genetics
MH  - Insulin/*pharmacology
MH  - Kinetics
MH  - Liver Neoplasms
MH  - MAP Kinase Signaling System
MH  - Osmolar Concentration
MH  - *Phosphoprotein Phosphatases
MH  - Protein Phosphatase 1
MH  - Protein Tyrosine Phosphatases/biosynthesis/*genetics
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
PMC - PMC1223301
EDAT- 2003/01/17 04:00
MHDA- 2003/07/04 05:00
PMCR- 2003/10/15
CRDT- 2003/01/17 04:00
PHST- 2003/01/15 00:00 [accepted]
PHST- 2003/01/10 00:00 [revised]
PHST- 2002/08/29 00:00 [received]
PHST- 2003/01/17 04:00 [pubmed]
PHST- 2003/07/04 05:00 [medline]
PHST- 2003/01/17 04:00 [entrez]
PHST- 2003/10/15 00:00 [pmc-release]
AID - BJ20021357 [pii]
AID - 10.1042/BJ20021357 [doi]
PST - ppublish
SO  - Biochem J. 2003 Apr 15;371(Pt 2):609-19. doi: 10.1042/BJ20021357.