title: Skin Aging-Dependent Activation of the PI3K Signaling Pathway via Downregulation of PTEN Increases Intracellular ROS in Human Dermal Fibroblasts.
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.
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Eun-Mi
authors.identifier: 0000-0003-3782-8779
authors.initials: EM
authors.lastname: Noh
authors.affiliation: Division of Hematology/Oncology, Gachon University Gil Medical Center, Incheon 405-760, Republic of Korea.
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Microbiology & Immunology, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Hwa-Ryung
authors.initials: HR
authors.lastname: Song
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Jeong-Mi
authors.identifier: 0000-0002-7517-7586
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Minok
authors.initials: M
authors.lastname: Lee
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Hyun-Kyung
authors.identifier: 0000-0002-9472-0724
authors.initials: HK
authors.lastname: Song
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: On-Yu
authors.initials: OY
authors.lastname: Hong
authors.affiliation: Department of Pediatrics, Institute of Clinical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Pyoung H
authors.initials: PH
authors.lastname: Whang
authors.affiliation: Department of Microbiology & Immunology, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Han
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea; Department of Korean Physiology, Wonkwang University School of Korean Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Jong-Suk
authors.identifier: 0000-0002-2309-8499
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea; Department of Oral Biochemistry and Institute of Biomaterials, Implant, School of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Young-Rae
authors.identifier: 0000-0002-2119-2609
authors.initials: YR
authors.lastname: Lee
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D015536:Down-Regulation; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology* / Q000473:pathology; D015595:Skin Aging; D013997:Time Factors; D014162:Transfection
chemical_list: D018129:Phosphatidylinositol Phosphates; D017382:Reactive Oxygen Species; C060974:phosphatidylinositol 3,4,5-triphosphate; D019255:NADPH Oxidases; D058539:Phosphatidylinositol 3-Kinase; D051744:Protein Kinase C-epsilon; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human