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

被引:68
作者
Deng, WL [1 ]
Wang, D [1 ]
Gosmanova, E [1 ]
Johnson, LR [1 ]
Tigyi, G [1 ]
机构
[1] Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2003年 / 284卷 / 05期
关键词
lysophosphatidic acid; camptothecin; cytochrome c; Bcl-2; protein; caspase-9; caspase-3/cpp32;
D O I
10.1152/ajpgi.00406.2002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 G(i)-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.
引用
收藏
页码:G821 / G829
页数:9
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