Age-associated reduction of cell spreading induces mitochondrial DNA common deletion by oxidative stress in human skin dermal fibroblasts: implication for human skin connective tissue agingReportar como inadecuado




Age-associated reduction of cell spreading induces mitochondrial DNA common deletion by oxidative stress in human skin dermal fibroblasts: implication for human skin connective tissue aging - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Biomedical Science

, 22:62

First Online: 28 July 2015Received: 16 April 2015Accepted: 10 July 2015DOI: 10.1186-s12929-015-0167-6

Cite this article as: Quan, C., Cho, M.K., Perry, D. et al. J Biomed Sci 2015 22: 62. doi:10.1186-s12929-015-0167-6

Abstract

BackgroundReduced cell spreading is a prominent feature of aged dermal fibroblasts in human skin in vivo. Mitochondrial DNA mtDNA common deletion has been reported to play a role in the human aging process, however the relationship between age-related reduced cell spreading and mtDNA common deletion has not yet been reported.

ResultsTo examine mtDNA common deletion in the dermis of aged human skin, the epidermis was removed from full-thickness human skin samples using cryostat. mtDNA common deletion was significantly elevated in the dermis of both naturally aged and photoaged human skin in vivo. To examine the relationship between age-related reduced cell spreading and mtDNA common deletion, we modulated the shape of dermal fibroblasts by disrupting the actin cytoskeleton. Reduced cell spreading was associated with a higher level of mtDNA common deletion and was also accompanied by elevated levels of endogenous reactive oxygen species ROS. Boosting cellular antioxidant capacity by using antioxidants was found to be protective against mtDNA common deletion associated with reduced cell spreading.

ConclusionmtDNA common deletion is highly prevalent in the dermis of both naturally aged and photoaged human skin in vivo. mtDNA common deletion in response to reduced cell spreading is mediated, at least in part, by elevated oxidative stress in human dermal fibroblasts. These data extend current understanding of the mitochondrial theory of aging by identifying the connection between mtDNA common deletion and age-related reduction of cell spreading.

KeywordsCell shape Mitochondrial common deletion Reactive oxygen species Human skin connective tissue aging AbbreviationsmtDNAmitochondrial DNA

Lat-ALatrunculin-A

ROSReactive oxygen species

NACN-acetyl-cysteine

UVUltraviolet

COL-1type I collagen

K14Keratin 14

MMP-1Matrix metalloproteinase 1

ECMExtracellular matrix

PCRPolymerase chain reaction

AP-1Activator protein-1

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Autor: Chunji Quan - Moon Kyun Cho - Daniel Perry - Taihao Quan

Fuente: https://link.springer.com/







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