LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway

Wenlin Deng, De An Wang, Elvira Gosmanova, Leonard R. Johnson, Gabor Tigyi

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume284
Issue number5 47-5
StatePublished - May 1 2003

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Epithelial Cells
Apoptosis
Caspase 9
Caspase 3
Cytochromes c
Mitochondria
lysophosphatidic acid
Camptothecin
Messenger RNA
Proteins
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Caspase Inhibitors
Pertussis Toxin
DNA Fragmentation
Gastroenterology
Cytosol
Up-Regulation
Phosphorylation
Peptides

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway. / Deng, Wenlin; Wang, De An; Gosmanova, Elvira; Johnson, Leonard R.; Tigyi, Gabor.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 284, No. 5 47-5, 01.05.2003.

Research output: Contribution to journalArticle

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