Cellular lipid peroxidation end-products induce apoptosis in human lens epithelial cells

S. Choudhary, W. Zhang, F. Zhou, Gerald Campbell, L. L. Chan, E. B. Thompson, Naseem Ansari

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Hydrogen peroxide (H2O2), an oxidant present in high concentrations in the aqueous humor of the elderly eyes, is known to impart toxicity to the lens - apoptosis being one of the toxic events. Since H2O2 causes lipid peroxidation leading to the formation of reactive end-products, it is important to investigate whether the end-products of lipid peroxidation are involved in the oxidation-induced apoptosis in the lens. 4-Hydroxynonenal (HNE), a major cytotoxic end product of lipid peroxidation, has been shown to mediate oxidative stress-induced cell death in many cell types. It has been shown that HNE is cataractogenic in micromolar concentrations in vitro, however, the underlying mechanism is not yet clearly understood. In the present study we have demonstrated that H2O2 and the lipid derived aldehydes, HNE and 4-hydroxyhexenal (HHE), can induce dose- and time-dependent loss of cell viability and a simultaneous increase in apoptosis involving activation of caspases such as caspase-1, -2, -3, and -8 in the cultured human lens epithelial cells. Interestingly, we observed that Z-VAD, a broad range inhibitor of caspases, conferred protection against H2O2- and HNE-induced apoptosis, suggesting the involvement of caspases in this apoptotic system. Using the cationic dye JC-1, early apoptotic changes were assessed following 5 h of HNE and H2O2 insult. Though HNE exposure resulted in ∼ 50% cells to undergo early apoptotic changes, no such changes were observed in H2O2 treated cells during this period. Furthermore, apoptosis, as determined by quantifying the DNA fragmentation, was apparent at a much earlier time period by HNE as opposed to H2O2. Taken together, the results demonstrate the apoptotic potential of the lipid peroxidation end-products and suggest that H2O2-induced apoptosis may be mediated by these end-products in the lens epithelium.

Original languageEnglish (US)
Pages (from-to)360-369
Number of pages10
JournalFree Radical Biology and Medicine
Volume32
Issue number4
DOIs
StatePublished - Feb 15 2002

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Keywords

  • 4-Hydroxynonenal
  • Apoptosis
  • Cataract
  • Free radicals
  • Human lens epithelial cells
  • Hydrogen peroxide
  • Oxidative damage

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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