KMID : 1101720140180030259
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Physical Activity and Nutrition 2014 Volume.18 No. 3 p.259 ~ p.266
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NAMPT regulates mitochondria biogenesis via NAD metabolism and calcium binding proteins during skeletal muscle contraction
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Kim Jeong-Seok
Yoon Chung-Su Park Dae-Ryoung
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Abstract
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[Purpose] The purpose of this study was to investigate the effect that muscle contraction induced NAD metabolism via NAMPT has on mitochondrial biogenesis.
[Methods] Primary skeletal muscle cells were isolated from the gastrocnemius in C57BL/6 mice. The muscle cells were stimulated by electrical current at 1Hz for 3 minutes in conditions of normal or NAD metabolism related inhibitor treatment. NAD/NADH level, Sirt1 and mitochondria biogenesis related signal factor¡¯s changes were examined in normal or NAD metabolism related inhibitor treated cells.
[Results] Electrical stimulation (ES) induced muscle contractions significantly increased NAD/NADH levels, NAMPT inhibitor FK-866 inhibited ES-induced NAD formation, which caused SIRT1 expression and PGC-1¥á deacetylation to decrease. Moreover, NAMPT inhibition decreased mitochondrial biogenesis related mRNA, COX-1 and Tfam levels. Along with AMPK inhibitor, compound C decreases SIRT1 expression, PGC-1¥á deacetylation and muscle contraction induced mitochondrial biogenesis related mRNA increment. These results indicated that the AMPK-NAMPT signal is a key player for muscle contraction induced SIRT1 expression and PGC-1¥á deacetylation, which influences mitochondrial biogenesis. Inhibition of the AMPK upregulator, Camkk¥â, STO-609 decreased AMPK phosphorylation and SIRT1 expression but did not decrease PGC-1¥á deacetylation. However, CAMKII inhibition via AIP decreased PGC-1¥á deacetylation.
[Conclusion] In conclusion, the results indicate that NAMPT plays an important role in NAD metabolism and mitochondrial biogenesis. However, mitochondrial biogenesis is also controlled by different calcium binding protein signals including Camkk¥â and CAMKII. [Keyword] Muscle contraction, NAD metabolism, SIRT1, PGC-1 ¥á, mitochondria biogenesis.
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KEYWORD
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Muscle contraction, NAD metabolism, SIRT1, PGC-1 ¥á, mitochondria biogenesis
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