Preventive effects of a water-soluble derivative of chroman moiety of vitamin E on lipid hydroperoxide-induced cell injuries and DNA cleavages through repressions of oxidative stress in the cytoplasm of human keratinocytes.
ChrCrx (6-hydroxy-2, 5, 7, 8-tetramethyl-chroman-2-carboxylic acid) is a water-soluble analog in which 4', 8', 12'-trimethyltridecyl chain is deleted from an alpha-tocopherol molecule known as a hydrophobic antioxidant. Cell viability of human skin epidermal keratinocytes HaCaT was lowered by treatment with tert-butylhydroperoxide (t-BuOOH) of 50 microM for 48 h, designated as a subacute cytotoxicity, which was prevented by previous administration with ChrCrx in a dose-dependent manner as estimated by mitochondrial function-based WST-1 assay and cell morphological microscopy. In contrast an acute cytotoxicity due to treatment with t-BuOOH as dense as 200 microM for a period as short as 2 h could be also prevented with ChrCrx that was administered before and after, but was eliminated during, treatment with t-BuOOH. In contrast alpha-tocopherol was not cytoprotective against t-BuOOH. DNA strand cleavages were induced with t-BuOOH in the keratinocytes, and could be prevented by ChrCrx more effectively than alpha-tocopherol as assayed by TUNEL stain. The intracellular reactive oxygen species (ROS) was accumulated in a manner dependent on periods of t-BuOOH treatment in the cytoplasm more abundantly rather than the nucleus of keratinocytes, and was markedly diminished by ChrCrx as shown by fluorography using the redox indicator dye. Thus t-BuOOH-induced cell injuries and DNA cleavages of the keratinocytes can be prevented at least in part through efficient diminishment of ROS generated in the cytoplasm, to which the preferred distribution of ChrCrx may be advantageous over to the nucleus or membrane owing to its molecular hydrophilicity relative to alpha-tocopherol.
Huang
Zhe
Z
Department of BioTechnology, Hiroshima Prefectural University School of BioSciences, Nanatsuka, Shobara, Hiroshima, Japan.
Senoh
Yuichiro
Y
Katoh
Shinya
S
Miwa
Nobuhiko
N
D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D002839:Chromans; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D014867:Water; D014810:Vitamin E; D020122:tert-Butylhydroperoxide; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid