L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis

0449794 - FGÚ 2016 RIV US eng J - Článek v odborném periodiku
Zelenka, Jaroslav - Dvořák, Aleš - Alán, Lukáš
L-Lactate Protects Skin Fibroblasts against Aging-Associated Mitochondrial Dysfunction via Mitohormesis.
Oxidative Medicine and Cellular Longevity. Roč. 2015, č. 2015 (2015), ID351698. ISSN 1942-0900. E-ISSN 1942-0994
Grant CEP: GA ČR(CZ) GPP305/12/P388
Institucionální podpora: RVO:67985823
Klíčová slova: mitochondria * reactive oxygen species * lactate * fibroblasts
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 4.492, rok: 2015

A moderate elevation of reactive oxygen species (ROS) production and a mild inhibition of mitochondrial respiratory chain have been associated with a health promotion and a lifespan extension in several animal models of aging. Here, we tested whether this phenomenon called mitohormesis could be mediated by l-lactate. The treatment with 5 mM l-lactate significantly increased H2O2 production and slightly inhibited the respiration in cultured skin fibroblasts and in isolated mitochondria. The l-lactate exposure was associated with oxidation of intracellular glutathione, phosphorylation of 5' AMP-activated protein kinase (AMPK), and induction of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1 alpha) transcription. A replicative aging of fibroblasts (L0) with a constant (LC), or intermittent 5 mM l-lactate (LI) in media showed that the high-passage LI fibroblasts have higher respiration, lower H2O2 release, and lower secretion of l-lactate compared to L0 and LC. This protection against mitochondrial dysfunction in LI cells was associated with lower activity of mechanistic target of rapamycin complex 1 (mTORC1), less signs of cellular senescence, and increased autophagy compared to L0 and LC. In conclusion, we demonstrated that intermittent but not constant exposure to l-lactate triggers mitohormesis, prevents aging-associated mitochondrial dysfunction, and improves other markers of aging
Trvalý link: http://hdl.handle.net/11104/0251978