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

被引:73
作者
Choudhary, S
Zhang, W
Zhou, F
Campbell, GA
Chan, LL
Thompson, EB
Ansari, NH
机构
[1] Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA
关键词
4-hydroxynonenal; human lens epithelial cells; apoptosis; cataract; oxidative damage; hydrogen peroxide; free radicals;
D O I
10.1016/S0891-5849(01)00810-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 14,0, 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 11,0, insult. Though HNE exposure resulted in similar to 50% cells to undergo early apoptotic changes, no such changes were observed in 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. (C) 2002 Elsevier Science Inc.
引用
收藏
页码:360 / 369
页数:10
相关论文
共 35 条
  • [1] Human ICE/CED-3 protease nomenclature
    Alnemri, ES
    Livingston, DJ
    Nicholson, DW
    Salvesen, G
    Thornberry, NA
    Wong, WW
    Yuan, JY
    [J]. CELL, 1996, 87 (02) : 171 - 171
  • [2] ANDLEY UP, 1994, INVEST OPHTH VIS SCI, V35, P3094
  • [3] Ansari N. H., 1997, Investigative Ophthalmology and Visual Science, V38, pS1171
  • [4] ANSARI NH, 1996, BIOCHEM MOL MED, V58, P2
  • [5] Failure to withstand oxidative stress induced by phospholipid hydroperoxides as a possible cause of the lens opacities in systemic diseases and ageing
    Babizhayev, MA
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1996, 1315 (02): : 87 - 99
  • [6] INHIBITION OF C-MYC EXPRESSION INDUCED BY 4-HYDROXYNONENAL, A PRODUCT OF LIPID-PEROXIDATION, IN THE HL-60 HUMAN LEUKEMIC-CELL LINE
    BARRERA, G
    MURACA, R
    PIZZIMENTI, S
    SERRA, A
    ROSSO, C
    SAGLIO, G
    FARACE, MG
    FAZIO, VM
    DIANZANI, MU
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1994, 203 (01) : 553 - 561
  • [7] CHRISTEN W, 1994, AM J MED, V97, pS22
  • [8] ANTIOXIDANTS AND EYE DISEASE
    CHRISTEN, WG
    [J]. AMERICAN JOURNAL OF MEDICINE, 1994, 97 : S14 - S17
  • [9] CHYLACK LT, 1984, OPHTHALMOLOGY, V91, P596
  • [10] Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells
    Ebinuma, H
    Saito, H
    Kosuga, M
    Wakabayashi, K
    Saito, Y
    Takagi, T
    Nakamoto, N
    Okuyama, T
    Ishii, H
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2001, 188 (01) : 56 - 66