Bovine-derived MFG-E8 alleviating mitochondrial dysfunction via Akt/Sirt1/PGC-1α and MAPK/ERK signaling cascades

Oxidative stress-induced mitochondria dysfunction exerting a central role in aging-related sarcopenia. The aim of this study was to explore the regulatory effect of Milk Fat Globule Epidermal Growth Factor Ⅷ (MFG-E8) on mitochondrial dysfunction. The oxidative stress injured L6 cell model was established by Rotenone. The results demonstrated that MFG-E8 promoted oxidative stress-injured L6 cell proliferation in a dose-dependent manner. The mechanism of MFG-E8 in improving oxidative stress-injured L6 cell was related to its promotional capacity to the activities of ATP, nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide (NAD⁺/NADH) and mitochondrial membrane potential (MMP). Meanwhile, MFG-E8 could also decrease oxygen species (ROS), lactate dehydrogenase (LDH) and increase glutathione reduced/oxidized (GSH/GSSG). MFG-E8 could up-regulate the phosphorylation level of Akt and ERK via activating Akt/Sirt1/PGC-1α and MAPK/ERK signaling pathway cascades in L6 cells, and promote the mitochondrial biogenesis of L6 cells, thereby upregulating the mRNA expression of NDUFA9, SDHA, UQCRC2, ATP5a, Nrf1, Tfam and Sirt3 as well as down-regulating p53. This study elucidated the molecular mechanism of MFG-E8 in alleviating mitochondria dysfunction through the Akt/Sirt1/PGC-1α and MAPK/ERK Signaling Cascades.