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

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2016 Dec 23

PMID 28003865

Citations 18

Authors

Eun-Mi Noh

Jinny Park

Hwa-Ryung Song

Jeong-Mi Kim

Minok Lee

Hyun-Kyung Song

On-Yu Hong

Pyoung H Whang

Myung-Kwan Han

Kang-Beom Kwon

Jong-Suk Kim

Young-Rae Lee

Affiliations

Soon will be listed here.

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.

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References

Shalev N, Wong M, Mills G, Yount G, Stokoe D . Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to mutation of the tumor suppressor PTEN/MMAC. Curr Biol. 1998; 8(21):1195-8. DOI: 10.1016/s0960-9822(07)00493-9. View

Hirai T, Chida K . Protein kinase Czeta (PKCzeta): activation mechanisms and cellular functions. J Biochem. 2003; 133(1):1-7. DOI: 10.1093/jb/mvg017. View

Zhang G, Wu L, Dai T, Chen S, Wang A, Lin K . NADPH oxidase-2 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis. Exp Dermatol. 2014; 23(9):639-44. DOI: 10.1111/exd.12479. View

Makrantonaki E, Zouboulis C . William J. Cunliffe Scientific Awards. Characteristics and pathomechanisms of endogenously aged skin. Dermatology. 2007; 214(4):352-60. DOI: 10.1159/000100890. View

Chen Q, Fischer A, Reagan J, Yan L, Ames B . Oxidative DNA damage and senescence of human diploid fibroblast cells. Proc Natl Acad Sci U S A. 1995; 92(10):4337-41. PMC: 41939. DOI: 10.1073/pnas.92.10.4337. View

Campisi J . Aging, cellular senescence, and cancer. Annu Rev Physiol. 2012; 75:685-705. PMC: 4166529. DOI: 10.1146/annurev-physiol-030212-183653. View

Myers M, Pass I, Batty I, van der Kaay J, Stolarov J, Hemmings B . The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci U S A. 1998; 95(23):13513-8. PMC: 24850. DOI: 10.1073/pnas.95.23.13513. View

Bedard K, Krause K . The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007; 87(1):245-313. DOI: 10.1152/physrev.00044.2005. View

Kurose K, Zhou X, Araki T, Cannistra S, Maher E, Eng C . Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol. 2001; 158(6):2097-106. PMC: 1891985. DOI: 10.1016/S0002-9440(10)64681-0. View

10.

Niswender K, Gallis B, Blevins J, Corson M, Schwartz M, Baskin D . Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin. J Histochem Cytochem. 2003; 51(3):275-83. DOI: 10.1177/002215540305100302. View

11.

Tarpey M, Fridovich I . Methods of detection of vascular reactive species: nitric oxide, superoxide, hydrogen peroxide, and peroxynitrite. Circ Res. 2001; 89(3):224-36. DOI: 10.1161/hh1501.094365. View

12.

Hutter E, Unterluggauer H, Uberall F, Schramek H, Jansen-Durr P . Replicative senescence of human fibroblasts: the role of Ras-dependent signaling and oxidative stress. Exp Gerontol. 2002; 37(10-11):1165-74. DOI: 10.1016/s0531-5565(02)00136-5. View

13.

Bae Y, Sung J, Kim O, Kim Y, Hur K, Kazlauskas A . Platelet-derived growth factor-induced H(2)O(2) production requires the activation of phosphatidylinositol 3-kinase. J Biol Chem. 2000; 275(14):10527-31. DOI: 10.1074/jbc.275.14.10527. View

14.

Hayflick L . THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS. Exp Cell Res. 1965; 37:614-36. DOI: 10.1016/0014-4827(65)90211-9. View

15.

Chen Q, Prowse K, Tu V, Purdom S, Linskens M . Uncoupling the senescent phenotype from telomere shortening in hydrogen peroxide-treated fibroblasts. Exp Cell Res. 2001; 265(2):294-303. DOI: 10.1006/excr.2001.5182. View

16.

Fisher G, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S . Mechanisms of photoaging and chronological skin aging. Arch Dermatol. 2002; 138(11):1462-70. DOI: 10.1001/archderm.138.11.1462. View

17.

Dang P, Fontayne A, Hakim J, El Benna J, Perianin A . Protein kinase C zeta phosphorylates a subset of selective sites of the NADPH oxidase component p47phox and participates in formyl peptide-mediated neutrophil respiratory burst. J Immunol. 2001; 166(2):1206-13. DOI: 10.4049/jimmunol.166.2.1206. View

18.

Jenkins G . Molecular mechanisms of skin ageing. Mech Ageing Dev. 2002; 123(7):801-10. DOI: 10.1016/s0047-6374(01)00425-0. View

19.

Ono Y, Fujii T, Ogita K, Kikkawa U, Igarashi K, NISHIZUKA Y . Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties. Proc Natl Acad Sci U S A. 1989; 86(9):3099-103. PMC: 287072. DOI: 10.1073/pnas.86.9.3099. View

20.

Kohl E, Steinbauer J, Landthaler M, Szeimies R . Skin ageing. J Eur Acad Dermatol Venereol. 2011; 25(8):873-84. DOI: 10.1111/j.1468-3083.2010.03963.x. View