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

David W Li, Hua Xiang, Ying Wei Mao, Juan Wang, Uwe Fass, Xin Yuan Zhang, Chong Xu

Research output: Contribution to journalArticle

60 Citations (Scopus)

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

Keywords

  • Apoptosis
  • Caspase-3
  • Caspase-3 inhibitor
  • Gene expression
  • Lens αB crystallin
  • N/N1003A
  • Okadaic acid
  • Rat lens epithelial cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

Li, D. W., Xiang, H., Mao, Y. W., Wang, J., Fass, U., Zhang, X. Y., & Xu, C. (2001). Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. Experimental Cell Research, 266(2), 279-291. https://doi.org/10.1006/excr.2001.5223

Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. / Li, David W; Xiang, Hua; Mao, Ying Wei; 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

Li, DW, Xiang, H, Mao, YW, Wang, J, Fass, U, Zhang, XY & Xu, C 2001, 'Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis', Experimental Cell Research, vol. 266, no. 2, pp. 279-291. https://doi.org/10.1006/excr.2001.5223
Li, David W ; Xiang, Hua ; Mao, Ying Wei ; 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.
@article{dc238c3aac4f4d8c9aa1e68699d1ffb7,
title = "Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis",
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.",
keywords = "Apoptosis, Caspase-3, Caspase-3 inhibitor, Gene expression, Lens αB crystallin, N/N1003A, Okadaic acid, Rat lens epithelial cells",
author = "Li, {David W} and Hua Xiang and Mao, {Ying Wei} and Juan Wang and Uwe Fass and Zhang, {Xin Yuan} and Chong Xu",
year = "2001",
month = "1",
day = "1",
doi = "10.1006/excr.2001.5223",
language = "English (US)",
volume = "266",
pages = "279--291",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis

AU - Li, David W

AU - Xiang, Hua

AU - Mao, Ying Wei

AU - Wang, Juan

AU - Fass, Uwe

AU - Zhang, Xin Yuan

AU - Xu, Chong

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Caspase-3

KW - Caspase-3 inhibitor

KW - Gene expression

KW - Lens αB crystallin

KW - N/N1003A

KW - Okadaic acid

KW - Rat lens epithelial cells

UR - http://www.scopus.com/inward/record.url?scp=0034954056&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034954056&partnerID=8YFLogxK

U2 - 10.1006/excr.2001.5223

DO - 10.1006/excr.2001.5223

M3 - Article

VL - 266

SP - 279

EP - 291

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 2

ER -