Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis

David Wan Cheng Li, Hua Xiang, Yingwei Mao, Juan Wang, Uwe Fass, Xin Yuan Zhang, Chong Xu

Research output: Contribution to journalArticle

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Abstract

Phosphorylation and dephosphorylation are important cellular events regulating major metabolic activities such as signal transduction, gene expression, cell cycle progression, and apoptosis. It is well documented that okadaic acid, a potent inhibitor of protein phosphatase-1 (PP-1) and -2A (PP-2A), can induce apoptosis in a variety of cell lines. Our recent studies have revealed that in the immortal rabbit lens epithelial cell line, N/N1003A, inhibition of PP-1, but not PP-2A, leads to rapid apoptosis of the lens epithelial cells. This induction of cell death is associated with up-regulated expression of a set of genes, including the tumor-suppressor gene, p53, and the proapoptotic gene, bax. In the present study, we demonstrate that inhibition of PP-1 by okadaic acid in the primary cultures of rat lens epithelial cells also leads to apoptotic death. Moreover, we show that the cysteine protease, caspase-3, is important in the execution of okadaic acid-induced apoptosis. Treatment of the primary cultures of rat lens epithelial cells with 100 nM okadaic acid up-regulates expression of caspase-3 at the mRNA, protein, and enzyme activity levels. Inhibition of the caspase-3 activity with a chemically synthesized inhibitor prevents okadaic acid-induced apoptosis in rat lens epithelial cells. Similar results are also observed in the immortal cell line N/N1003A. Furthermore, stable expression of the mouse gene encoding lens αB crystallin inhibits okadaic acid-induced apoptosis, and this inhibition is associated with repression of the okadaic acid-induced up-regulation of caspase-3 activity. Taken together, these results demonstrate that caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis.

Original languageEnglish (US)
Pages (from-to)279-291
Number of pages13
JournalExperimental Cell Research
Volume266
Issue number2
DOIs
StatePublished - Jan 1 2001

Fingerprint

Okadaic Acid
Caspase 3
Lenses
Epithelial Cells
Apoptosis
Protein Phosphatase 1
Cell Line
Up-Regulation
Gene Expression
Crystallins
Cysteine Proteases
p53 Genes
Tumor Suppressor Genes
Signal Transduction
Cell Cycle
Cell Death
Phosphorylation
Rabbits
Messenger RNA
Enzymes

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Li, David Wan Cheng ; Xiang, Hua ; Mao, Yingwei ; Wang, Juan ; Fass, Uwe ; Zhang, Xin Yuan ; Xu, Chong. / Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. In: Experimental Cell Research. 2001 ; Vol. 266, No. 2. pp. 279-291.
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Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. / Li, David Wan Cheng; Xiang, Hua; Mao, Yingwei; Wang, Juan; Fass, Uwe; Zhang, Xin Yuan; Xu, Chong.

In: Experimental Cell Research, Vol. 266, No. 2, 01.01.2001, p. 279-291.

Research output: Contribution to journalArticle

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