Epigallocatechin Gallate Reduces Slow-Twitch Muscle Fiber Formation and Mitochondrial Biosynthesis in C2C12 Cells by Repressing AMPK Activity and PGC-1α Expression

Abstract

Epigallocatechin gallate (EGCG) is a major active compound in green tea polyphenols. EGCG acts as an antioxidant to prevent the cell damage caused by free radicals and their derivatives. In skeletal muscle, exercise causes the accumulation of intracellular reactive oxygen species (ROS) and promotes the formation of slow-type muscle fiber. To determine whether EGCG, as a ROS scavenger, has any effect on skeletal muscle fiber type, we applied different concentrations (0, 5, 25, and 50 μM) of EGCG in the culture medium of differentiated C2C12 cells for 2 days. The fiber-type composition, mitochondrial biogenesis-related gene expression, antioxidant and glucose metabolism enzyme activity, and ROS levels in C2C12 cells were then detected. According to our results, 5 μM EGCG significantly decreased the cellular activity of SDH, 25 μM EGCG significantly downregulated the MyHC I, PGC-1α, NRF-1, and p-AMPK levels and SDH activity while enhancing the CAT and GSH-Px activity and decreasing the intracellular ROS levels, and 50 μM EGCG significantly downregulated MyHC I, PGC-1α, and NRF-1 expression and HK and SDH activity while increasing LDH activity. Furthermore, 300 μM H2O2 and 0.5 mM AMPK agonist (AICAR) improved the expression of MyHC I, PGC-1α, and p-AMPK, which were all reversed by 25 μM EGCG. In conclusion, the effect of EGCG on C2C12 cells may occur through the reduction of the ROS level, thereby decreasing both AMPK activity and PGC-1α expression and eventually reducing slow-twitch muscle fiber formation and mitochondrial biosynthesis.

Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway

“…Such skeletal muscle cell death plays a crucial role in the development of muscle atrophy, and the elevation of ROS levels is related to the degree of skeletal muscle cell damage in atrophic conditions (Zuo and Pannell 2015;Gao et al 2018). Recently, H 2 O 2 -induced oxidative stress has been shown to induce functional impairment of mitochondria, which can lead to myoblast damage (Wang et al 2016;Kim and Yi 2018;Ábrigo et al 2018). Thus, these observations suggest that the prevention of myoblast death by oxidative stress may be a promising strategy to prevent skeletal muscle wasting.…”

Epigallocatechin Gallate Modulates Muscle Homeostasis in Type 2 Diabetes and Obesity by Targeting Energetic and Redox Pathways: A Narrative Review

“…EGCG acts as a potent antioxidant and protects against oxidant agents such as docosahexaenoic acid (DHA) in in vitro experiments by decreasing ROS levels and restring changes in mitochondrial morphology induced by DHA [109]. Moreover, other experiments with mouse C2C12 muscle cells treated with EGCG have shown a reduction in ROS levels [110,111], and a beneficial effect on fatty acid-induced peripheral insulin resistance [112]. There are many mechanisms involved in such response including: inhibition of PKC activation enhanced by the AMPK cascade, IRS1 serine phosphorylation and other kinases such as ERK1/2 and p38 MAPK, essential for maximal stimulation of glucose uptake in response to insulin [113,114]; and finally, the suppression of lipid accumulation via the AMPK/ACC signaling pathway [112,115].…”

Bioactive food and exercise in chronic kidney disease: Targeting the mitochondria

“…Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound present in green tea (Camellia sinensis Theaceae) that may modulate mitochondrial function and control bioenergetics. 72,73 However, the exact effects of the catechin EGCGs, for example to what extent it induces MB, is still largely unknown, but studies have postulated that it acts as a powerful antioxidant and ROS scavenger. 74 Although abundant evidence supports the efficiency of EGCGs as antioxidants in in vitro studies, the evidence for effects in vivo is still lacking.…”