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

Autor: Shohei Morita, Reina Maruyama, Yoshiya Tome, Rahul Sharma, Yasushi Kawamai, Haruna Ueda, Naoya Yahagi, Takehito Sugasawa, Yoshinori Takeuchi, Kazuhiro Takekoshi, Yuichi Aita, Kaoru Takeuchi, Yasuko Yoshida
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
Response element
Cryotherapy
lcsh:Chemistry
Mice
0302 clinical medicine
Cyclic AMP
Phosphorylation
lcsh:QH301-705.5
Spectroscopy
biology
Chemistry
CREB
General Medicine
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Computer Science Applications
Cell biology
mitochondria
medicine.anatomical_structure
CREB1
transcription
Signal Transduction
Transcriptional Activation
Article
Catalysis
Inorganic Chemistry
03 medical and health sciences
In vivo
medicine
Animals
Physical and Theoretical Chemistry
Muscle
Skeletal
Molecular Biology
Pgc-1α
Organic Chemistry
Skeletal muscle
Cyclic AMP-Dependent Protein Kinases
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Mitochondrial biogenesis
Mice
Inbred CBA
biology.protein
gene expression
icing
cryotherapy
030217 neurology & neurosurgery
Ex vivo
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 13
International Journal of Molecular Sciences, Vol 21, Iss 4588, p 4588 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21134588
Popis: 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.
Databáze: OpenAIRE
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