Expression and regulation of glutathione S-transferase P1-1 in cultured human epidermal cells.
Six families of glutathione S-transferases (GSTs), which play an important role in cellular detoxification, are identified in human cells. We report that human keratinocytes and melanocytes express significant levels of GST activity, for which GSTP1-1 is mainly responsible. But, in contrast to previous reports that GSTP1-1 level increases in skin tumor tissues, GSTP1-1 expression does not increase in transformed keratinocytes and melanocytes in culture. Although the human GSTP1 gene carries in its 5'-flanking region multiple copies of the antioxidant response element (ARE), no increase in GSTP1-1 expression was observed after treatment of human keratinocytes (HaCaT) with ARE-mediated inducers. ARE is a cis-acting DNA element and stimulates the transcription of many genes. While studies suggest that an NF-kappaB binding site in the promoter region might suppress the ARE function, such a mechanism does not appear to exist in HaCaT cells. Moreover, although ras has been shown to stimulate the expression of human GSTP1-1, the effect of c-Ha-ras on GSTP1-1 expression in HaCaT cells appears limited.
Zhang
Yuesheng
Y
Department of Medicine, College of Medicine, Arizona Cancer Center, University of Arizona, Room 4985A, 1515 N Campbell Avenue, Tucson, AZ 85724, USA. yzhang@azcc.arizona.edu
Gonzalez
Veronica
V
Xu
Min Jian
MJ
D000975:Antioxidants; D002460:Cell Line; D004817:Epidermis / Q000201:enzymology*; D015870:Gene Expression / Q000502:physiology; D011905:Genes, ras; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D012878:Skin Neoplasms / Q000201:enzymology
D000975:Antioxidants; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase