Curcumin induces mitochondrial biogenesis by increasing cyclic AMP levels via phosphodiesterase 4A inhibition in skeletal muscle

Abstract

Background: Previous research has suggested that curcumin potentially induces mitochondrial biogenesis in skeletal muscle via increasing cAMP levels. However, the regulatory mechanisms for this phenomenon remain unknown. The purpose of the present study was to clarify the mechanism by which curcumin activates cAMP-related signalling pathways that upregulate mitochondrial biogenesis and respiration in skeletal muscle. Methods: The effect of curcumin treatment (i.p., 100 mg/kg-BW/day for 28 days) on mitochondrial biogenesis was determined in rats. The effects of curcumin and exercise (swimming for 2 h/day for 3 days) on the cAMP signalling pathway were determined in the absence and presence of phosphodiesterase (PDE) or protein kinase A (PKA) inhibitors. Mitochondrial respiration, citrate synthase (CS) activity, cAMP content, and protein expression of cAMP/PKA signalling molecules were analysed. Results: Curcumin administration increased COX-IV protein expression, and CS and complex I activity, consistent with the induction of mitochondrial biogenesis by curcumin. Mitochondrial respiration was not altered by curcumin treatment. Curcumin and PDE inhibition tended to increase cAMP levels with or without exercise. In addition, exercise increased the phosphorylation of PDE4A, whereas curcumin treatment strongly inhibited PDE4A phosphorylation regardless of exercise. Furthermore, curcumin promoted AMPK phosphorylation and PGC-1α deacetylation. Inhibition of PKA abolished the phosphorylation of AMPK. Conclusion: The present results suggest that curcumin increases cAMP levels via inhibition of PDE4A phosphorylation, which induces mitochondrial biogenesis through a cAMP/PKA/AMPK signalling pathway. Our data also suggest the possibility that curcumin utilizes a regulatory mechanism for mitochondrial biogenesis that is distinct from the exercise-induced mechanism in skeletal muscle.

Next-Generation Ultrasol Curcumin Boosts Muscle Endurance and Reduces Muscle Damage in Treadmill-Exhausted Rats

“…Acute exercise stimulates the PGC-1α in rodents and humans, and it helps to modulate muscle autophagy [ 27 ]. Although the previous studies reported that curcumin supplementation increased the PGC-1α protein levels or deacetylation in muscle tissue [ 13 , 28 , 29 ], we found that NGUC supplementation suppresses the muscle PGC-1α levels after one-time exhaustive exercise. Kang, et al [ 30 ] reported that attenuating the ROS releasing with allopurinol, an antioxidant, decreased the muscle PGC-1α levels following acute exercise.…”

Emerging Role of cAMP/AMPK Signaling

“…As a result, mitochondrial biogenesis and function are improved, which in turn protects against diet-induced obesity and glucose intolerance in mice. In line with these findings, Hamidie et al [ 74 ] have recently shown that intraperitoneal curcumin treatment in rats increased cAMP levels in muscle due to the inhibition of PDE4A. As a consequence, activation of the PKA-LKB1 axis followed by phosphorylation of AMPK and deacetylation of PGC-1α leads to the induction of mitochondrial biogenesis in skeletal muscle.…”

Anti-Cancer Effects of Dietary Polyphenols via ROS-Mediated Pathway with Their Modulation of MicroRNAs

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