RRC ID 63407
著者 Sugasawa T, Tome Y, Takeuchi Y, Yoshida Y, Yahagi N, Sharma R, Aita Y, Ueda H, Maruyama R, Takeuchi K, Morita S, Kawamai Y, Takekoshi K.
タイトル Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy.
ジャーナル Int J Mol Sci
Abstract Local cryotherapy is widely used as a treatment for sports-related skeletal muscle injuries. The molecular mechanisms are unknown. To clarify these mechanisms, we applied one to three 15-min cold stimulations at 4 °C to various cell lines (in vitro), the tibialis anterior (TA) muscle (ex vivo), and mouse limbs (in vivo). In the in vitro assay, cyclic AMP (cAMP) response element binding protein 1 (CREB1) was markedly phosphorylated (p-CREB1), and the CREB-binding protein (CBP) was recruited to p-CREB-1 in response to two or three cold stimulations. In a reporter assay with the cAMP-responsive element, the signals significantly increased after two to three cold stimulations at 4 °C. In the ex vivo study, CREB-targeting genes were significantly upregulated following two or three cold stimulations. The in vivo experiment disclosed that cold stimulation of a mouse limb for 9 days significantly increased mitochondrial DNA copy number and upregulated genes involved in mitochondrial biogenesis. The results suggest that local cryotherapy increases CREB transcription and upregulates CREB-targeting genes, in a manner dependent on cold stimulation frequency and duration. This information will inform further investigations into local cryotherapy as a treatment for sports-related skeletal muscle trauma.
巻・号 21(13)
公開日 2020-6-28
DOI 10.3390/ijms21134588
PII ijms21134588
PMID 32605164
PMC PMC7370117
MeSH Animals Cryotherapy / methods* Cyclic AMP / metabolism* Cyclic AMP-Dependent Protein Kinases / genetics Cyclic AMP-Dependent Protein Kinases / metabolism* Male Mice Mice, Inbred CBA Muscle, Skeletal / cytology Muscle, Skeletal / metabolism Muscle, Skeletal / physiology* Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism* Phosphorylation Signal Transduction Transcriptional Activation
IF 4.556
リソース情報
ヒト・動物細胞 C2C12(RCB0987)