UVA-induced metabolic changes in non-malignant skin cells and the potential role of pyruvate as antioxidant

Ivanova, I. and Bogner, C. and Gronwald, W. and Kreutz, M. and Kurz, B. and Maisch, T. and Kamenisch, Y. and Berneburg, M. (2023) UVA-induced metabolic changes in non-malignant skin cells and the potential role of pyruvate as antioxidant. PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 22 (8). pp. 1889-1899. ISSN 1474-905X, 1474-9092

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Abstract

The exposure to UVA (320-400 nm) irradiation is a major threat to human skin concerning photoaging and carcinogenesis. It has been shown that UVA irradiation can induce reactive oxygen species (ROS) and DNA mutations, such as 8-hydroxydeoxyguanosine. Furthermore, UVA induces the expression of photoaging-associated matrix metalloproteases (MMPs), especially of matrix metalloprotease 1 (MMP 1) and matrix metalloprotease 3 (MMP 3). In addition to this, it was recently shown that UVA-induced ROS also increase glucose metabolism of melanoma cells, however, the influence of UVA on the glucose metabolism of non-malignant cells of the human skin has, so far, not been investigated in detail. Here, we investigated the UVA-induced changes in glucose metabolism and the functional relevance of these changes in primary fibroblasts-normal non-malignant cells of the skin. These cells showed an UVA-induced enhanced glucose consumption and lactate production and changes in pyruvate production. As it has been proposed that pyruvate could have antioxidant properties we tested the functional relevance of pyruvate as protective agent against UVA-induced ROS. Our initial experiments support earlier publications, demonstrating that pyruvate treated with H2O2 is non-enzymatically transformed to acetate. Furthermore, we show that this decarboxylation of pyruvate to acetate also occurs upon UVA irradiation. In addition to this, we could show that in fibroblasts pyruvate has antioxidant properties as enhanced levels of pyruvate protect cells from UVA-induced ROS and partially from a DNA mutation by the modified base 8-hydroxydeoxyguanosine. Furthermore, we describe for the first time, that the interaction of UVA with pyruvate is relevant for the regulation of photoaging-associated MMP 1 and MMP 3 expression.

Item Type: Article
Uncontrolled Keywords: NONENZYMATIC DECARBOXYLATION; LACTIC-ACID; DEFENSE; STRESS; DAMAGE; DNA; Non-malignant dermal cells; Glucose metabolism; Ultraviolet (UV) radiation; Reactive oxygen species; MMP; Pyruvate
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Dermatologie und Venerologie
Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner)
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 08 Mar 2024 09:19
Last Modified: 08 Mar 2024 09:19
URI: https://pred.uni-regensburg.de/id/eprint/59055

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