RGD Reference Report - Tumor necrosis factor alpha triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation. - Rat Genome Database

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Tumor necrosis factor alpha triggers antiapoptotic mechanisms in rat pancreatic cells through pancreatitis-associated protein I activation.

Authors: Malka, D  Vasseur, S  Bodeker, H  Ortiz, EM  Dusetti, NJ  Verrando, P  Dagorn, JC  Iovanna, JL 
Citation: Malka D, etal., Gastroenterology. 2000 Sep;119(3):816-28.
RGD ID: 9831402
Pubmed: PMID:10982776   (View Abstract at PubMed)

BACKGROUND & AIMS: Tumor necrosis factor (TNF)-alpha contributes to the development of acute pancreatitis. Because TNF-alpha is involved in the control of apoptosis, we studied its interaction with the pancreatic apoptotic pathway. METHODS: Pancreatic acinar AR4-2J cells were used. Apoptosis was monitored by morphologic and biochemical criteria. RESULTS: TNF-alpha induced apoptosis in AR4-2J cells. Induction was strongly enhanced in cells treated with actinomycin D, suggesting that TNF-alpha activated concomitantly an antiapoptotic mechanism through newly synthesized proteins. This mechanism involved activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein (MAP) kinases because their inhibition worsened TNF-alpha-induced apoptosis. The antiapoptotic pancreatitis-associated protein (PAP) I is a candidate for mediating TNF-alpha activity. Its expression is induced by TNF-alpha, and cells overexpressing PAP I show significantly less apoptosis on exposure to TNF-alpha. We examined whether TNF-alpha induction of PAP I expression was mediated by NF-kappaB or MAP kinases by using specific inhibitors of both pathways. Inhibition of NF-kappaB had no effect. However, inhibitors of MEK1 eliminated PAP I induction. CONCLUSIONS: TNF-alpha induces concomitantly proapoptotic and antiapoptotic mechanisms in pancreatic AR4-2J cells. Antiapoptotic mechanisms are mediated by NF-kappaB and MAP kinases, and PAP I is one of the effectors of apoptosis inhibition.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to tumor necrosis factor  IEP 9831402 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Reg3b  (regenerating family member 3 beta)


Additional Information