LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway
In: American journal of physiology. Gastrointestinal and liver physiology, Jg. 47 (2003), Heft 5, S. G821- (9S.)
Online
academicJournal
- print, 71 ref
Zugriff:
We previously showed (Gastroenterology 123: 206-216, 2002) that lysophosphatidic acid (LPA) protects and rescues rat intestinal epithelial cells (IEC-6) from apoptosis. Here, we provide evidence for the LPA-elicited inhibition of the mitochondrial apoptotic pathway leading to attenuation of caspase-3 activation. Pretreatment of IEC-6 cells with LPA inhibited campothecin-induced caspase-9 and caspase-3 activation and DNA fragmentation. A caspase-9 inhibitor peptide mimicked the LPA-elicited antiapoptotic activity. LPA elicited ERK1/ ERK2 and PKB/Akt phosphorylation. The LPA-elicited antiapoptotic activity and inhibition of caspase-9 activity were abrogated by pertussis toxin, PD 98059, wortmannin, and LY 294002. LPA reduced cytochrome c release from mitochondria and prevented activation of caspase-9. LPA prevented translocation of Bax from cytosol to mitochondria and increased the expression of the antiapoptotic Bcl-2 mRNA and protein. LPA had no effect on Bcl-xl, Bad, and Bak mRNA or protein expression. These data indicate that LPA protects IEC-6 cells from camptothecin-induced apoptosis through Gi-coupled inhibition of caspase-3 activation mediated by the attenuation of caspase-9 activation due to diminished cytochrome c release, involving upregulation of Bcl-2 protein expression and prevention of Bax translocation.
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LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway
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Autor/in / Beteiligte Person: | DENG, Wenlin ; WANG, De-An ; GOSMANOVA, Elvira ; JOHNSON, Leonard R ; TIGYI, Gabor |
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Zeitschrift: | American journal of physiology. Gastrointestinal and liver physiology, Jg. 47 (2003), Heft 5, S. G821- (9S.) |
Veröffentlichung: | Bethesda, MD: American Physiological Society, 2003 |
Medientyp: | academicJournal |
Umfang: | print, 71 ref |
ISSN: | 0193-1857 (print) |
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