RGD Reference Report - Role of p38 map kinase in glycine-induced hepatocyte resistance to hypoxic injury. - Rat Genome Database

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Role of p38 map kinase in glycine-induced hepatocyte resistance to hypoxic injury.

Authors: Carini, R  Alchera, E  Baldanzi, G  Piranda, D  Splendore, R  Grazia De Cesaris, M  Caraceni, P  Graziani, A  Albano, E 
Citation: Carini R, etal., J Hepatol. 2007 Apr;46(4):692-9. Epub 2006 Nov 27.
RGD ID: 1642611
Pubmed: PMID:17188389   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jhep.2006.10.014   (Journal Full-text)

BACKGROUND/AIMS: Glycine hepatoprotection is well known. However, the mechanisms involved are still poorly characterized. METHODS: Glycine protection was investigated in isolated rat hepatocytes pretreated with 2 mmol/L glycine 15 min before incubation under hypoxic conditions. RESULTS: Glycine significantly reduced Na+ overload and hepatocyte death caused by hypoxia. Glycine protection required the activation of a signal pathway involving Src, Pyk2 and p38 MAP kinases. Glycine treatment also induced a 11% increase of hepatocyte volume and transient ATP release. The prevention of cell swelling by hepatocyte incubation in a hypertonic medium as well as the degradation of extracellular ATP with apyrase or the block P2 purinergic receptors with suramin reverted glycine-induced cytoprotection and inhibited Src, Pyk2 and p38 MAPK activation. Glycine down-modulated Na+/H+ exchanger (NHE) activity, without affecting the development of intracellular acidosis during hypoxia. Such an effect was reverted by inhibiting p38 MAPK that also abolished glycine protection against Na+ overload caused by hypoxia. CONCLUSIONS: Glycine-induced ATP release in response to a moderate hepatocyte swelling led to the autocrine stimulation of P2 receptors and to the activation of Src, Pyk2 and p38 MAPK that increased hepatocyte resistance to hypoxia by preventing Na+ influx through NHE.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPISrc (Rattus norvegicus)1642611 RGD 
protein binding  IPIPtk2b (Rattus norvegicus)1642611 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptk2b  (protein tyrosine kinase 2 beta)
Src  (SRC proto-oncogene, non-receptor tyrosine kinase)


Additional Information