Zelenka 2015 Oxid Med Cell Longev
| Zelenka J, DvoΕΓ‘k A, AlΓ‘n L (2015) L-lactate protects skin fibroblasts against aging-associated mitochondrial dysfunction via mitohormesis. Oxid Med Cell Longev 2015:351698. |
Zelenka J, Dvorak A, Alan L (2015) Oxid Med Cell Longev
Abstract: 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 5βmM 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 1Ξ± (PGC1Ξ±) transcription. A replicative aging of fibroblasts (L0) with a constant (LC), or intermittent 5βmM 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.
β’ O2k-Network Lab: CZ Prague Jezek P
Labels: MiParea: Respiration, mtDNA;mt-genetics
Pathology: Aging;senescence
Stress:Oxidative stress;RONS
Organism: Rat
Tissue;cell: Liver, Endothelial;epithelial;mesothelial cell, Fibroblast
Preparation: Intact cells, Isolated mitochondria
Coupling state: LEAK, ROUTINE, ET
Pathway: N, S
HRR: Oxygraph-2k
