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Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy

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...

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Autores principales: Sugasawa, Takehito, Tome, Yoshiya, Takeuchi, Yoshinori, Yoshida, Yasuko, Yahagi, Naoya, Sharma, Rahul, Aita, Yuichi, Ueda, Haruna, Maruyama, Reina, Takeuchi, Kaoru, Morita, Shohei, Kawamai, Yasushi, Takekoshi, Kazuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370117/
https://www.ncbi.nlm.nih.gov/pubmed/32605164
http://dx.doi.org/10.3390/ijms21134588
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author Sugasawa, Takehito
Tome, Yoshiya
Takeuchi, Yoshinori
Yoshida, Yasuko
Yahagi, Naoya
Sharma, Rahul
Aita, Yuichi
Ueda, Haruna
Maruyama, Reina
Takeuchi, Kaoru
Morita, Shohei
Kawamai, Yasushi
Takekoshi, Kazuhiro
author_facet Sugasawa, Takehito
Tome, Yoshiya
Takeuchi, Yoshinori
Yoshida, Yasuko
Yahagi, Naoya
Sharma, Rahul
Aita, Yuichi
Ueda, Haruna
Maruyama, Reina
Takeuchi, Kaoru
Morita, Shohei
Kawamai, Yasushi
Takekoshi, Kazuhiro
author_sort Sugasawa, Takehito
collection PubMed
description 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.
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spelling pubmed-73701172020-07-21 Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy Sugasawa, Takehito Tome, Yoshiya Takeuchi, Yoshinori Yoshida, Yasuko Yahagi, Naoya Sharma, Rahul Aita, Yuichi Ueda, Haruna Maruyama, Reina Takeuchi, Kaoru Morita, Shohei Kawamai, Yasushi Takekoshi, Kazuhiro Int J Mol Sci Article 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. MDPI 2020-06-28 /pmc/articles/PMC7370117/ /pubmed/32605164 http://dx.doi.org/10.3390/ijms21134588 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sugasawa, Takehito
Tome, Yoshiya
Takeuchi, Yoshinori
Yoshida, Yasuko
Yahagi, Naoya
Sharma, Rahul
Aita, Yuichi
Ueda, Haruna
Maruyama, Reina
Takeuchi, Kaoru
Morita, Shohei
Kawamai, Yasushi
Takekoshi, Kazuhiro
Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy
title Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy
title_full Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy
title_fullStr Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy
title_full_unstemmed Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy
title_short Influence of Intermittent Cold Stimulations on CREB and Its Targeting Genes in Muscle: Investigations into Molecular Mechanisms of Local Cryotherapy
title_sort influence of intermittent cold stimulations on creb and its targeting genes in muscle: investigations into molecular mechanisms of local cryotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370117/
https://www.ncbi.nlm.nih.gov/pubmed/32605164
http://dx.doi.org/10.3390/ijms21134588
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