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Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes.

ABSTRACT: In this study, we found a role for H(2)O(2) in UVA-induced AP-2alpha expression in the HaCaT human keratinocyte cell line. UVA irradiation not only increased AP-2alpha, but also caused accumulation of H(2)O(2) in the cell culture media, and H(2)O(2) by itself could induce the expression of AP-2alpha. By catalyzing the removal of H(2)O(2) from cells through over-expression of GPx-1, induction of AP-2alpha expression by UVA was abolished. Induction of transcription factor AP-2alpha by UVA had been previously shown to be mediated through the second messenger ceramide. We found that not only UVA irradiation, but also H(2)O(2) by itself caused increases of ceramide in HaCaT cells, and C2-ceramide added to cells induced the AP-2alpha signaling pathway. Finally, forced expression of GPx-1 eliminated UVA-induced ceramide accumulation as well as AP-2alpha expression. Taken together, these findings suggest that GPx-1 inhibits UVA-induced AP-2alpha expression by suppressing the accumulation of H(2)O(2).

SUBMITTER: Yu L

PROVIDER: S-EPMC1913288 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

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Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes.

Yu Lei L Venkataraman Sujatha S Coleman Mitchell C MC Spitz Douglas R DR Wertz Philip W PW Domann Frederick E FE

Biochemical and biophysical research communications 20061107 4

In this study, we found a role for H(2)O(2) in UVA-induced AP-2alpha expression in the HaCaT human keratinocyte cell line. UVA irradiation not only increased AP-2alpha, but also caused accumulation of H(2)O(2) in the cell culture media, and H(2)O(2) by itself could induce the expression of AP-2alpha. By catalyzing the removal of H(2)O(2) from cells through over-expression of GPx-1, induction of AP-2alpha expression by UVA was abolished. Induction of transcription factor AP-2alpha by UVA had been ...[more]

PMID: 17097614

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Project description:BackgroundGlutathione (GSH) is one of the most important agents of the antioxidant defense system of the cell because, in conjunction with the enzymes glutathione peroxidase (GSH-Px) and glutathione S transferase pi (GSTpi), it plays a central role in the detoxification and biotransformation of chemotherapeutic drugs. This study evaluated the expression of GSH and the GSH-Px and GSTpi enzymes by immunohistochemistry in 30 canine mammary tumors, relating the clinicopathological parameters, clinical outcome and survival of the bitches. In an in vitro study, the expression of the genes glutamate cysteine ligase (GCLC) and glutathione synthetase (GSS) that synthesize GSH and GSH-Px gene were verified by qPCR and subjected to treatment with doxorubicin, to check the resistance of cancer cells to chemotherapy.ResultsThe immunohistochemical expression of GSH, GSH-Px and GSTpi was compared with the clinical and pathological characteristics and the clinical outcome in the bitches, including metastasis and death.The results showed that high immunoexpression of GSH was correlated to the absence of tumor ulceration and was present in dogs without metastasis (P < 0.05). There was significant correlation of survival with the increase of GSH (P < 0.05). The expression of the GSH-Px and GSTpi enzymes showed no statistically significant correlation with the analyzed variables (p > 0.05). The analysis of the relative expression of genes responsible for the synthesis of GSH (GCLC and GSS) and GSH-Px by quantitative PCR was done with cultured cells of 10 tumor fragments from dogs with mammary tumors.The culture cells showed a decrease in GCLC and GSS expression when compared with no treated cells (P < 0.05). High GSH immunoexpression was associated with better clinical outcomes.ConclusionTherefore, high expression of the GSH seems to play an important role in the clinical outcome of patients with mammary tumors and suggest its use as prognostic marker. The in vitro doxorubicin treatment significantly reduces the expression of GCLC and GSS genes so we can consider them to be candidates for predictive markers of therapeutic response in mammary cancer.

Dataset Information

Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes.

Publications

Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes.

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