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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 6354261, 9 pages
http://dx.doi.org/10.1155/2016/6354261
Research Article

Skin Aging-Dependent Activation of the PI3K Signaling Pathway via Downregulation of PTEN Increases Intracellular ROS in Human Dermal Fibroblasts

1Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea
2Division of Hematology/Oncology, Gachon University Gil Medical Center, Incheon 405-760, Republic of Korea
3Department of Microbiology & Immunology, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea
4Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea
5Department of Pediatrics, Institute of Clinical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea
6Department of Korean Physiology, Wonkwang University School of Korean Medicine, Iksan 570-749, Republic of Korea
7Department of Oral Biochemistry and Institute of Biomaterials, Implant, School of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea

Received 25 March 2016; Revised 4 July 2016; Accepted 26 July 2016

Academic Editor: Juan F. Santibanez

Copyright © 2016 Eun-Mi Noh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Reactive oxygen species (ROS) play a major role in both chronological aging and photoaging. ROS induce skin aging through their damaging effect on cellular constituents. However, the origins of ROS have not been fully elucidated. We investigated that ROS generation of replicative senescent fibroblasts is generated by the modulation of phosphatidylinositol 3,4,5-triphosphate (PIP3) metabolism. Reduction of the PTEN protein, which dephosphorylates PIP3, was responsible for maintaining a high level of PIP3 in replicative cells and consequently mediated the activation of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway. Increased ROS production was blocked by inhibition of PI3K or protein kinase C (PKC) or by NADPH oxidase activating in replicative senescent cells. These data indicate that the signal pathway to ROS generation in replicative aged skin cells can be stimulated by reduced PTEN level. Our results provide new insights into skin aging-associated modification of the PI3K/NADPH oxidase signaling pathway and its relationship with a skin aging-dependent increase of ROS in human dermal fibroblasts.