Nonshivering thermogenesis protects against defective calcium handling in muscle

Autor: Andrew M. Bellinger, Jan Aydin, Jan Nedergaard, Andrew R. Marks, Håkan Westerblad, Shi-Jin Zhang, Barbara Cannon, Joseph D. Bruton, Steven Reiken, Irina G. Shabalina, Nicolas Place
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Adipose Tissue
Brown/metabolism
Acclimatization
Muscle Proteins
Biochemistry
Ion Channels
Research Communications
Mice
Adipose Tissue
Brown
Ion Channels/genetics/*metabolism
Brown adipose tissue
Phosphorylation
Uncoupling Protein 1
Mice
Knockout
Shivering
Muscle
Skeletal/*metabolism
Thermogenesis
Calcium/*metabolism
musculoskeletal system
Thermogenin
Mitochondrial Proteins/genetics/*metabolism
Cold Temperature
medicine.anatomical_structure
medicine.symptom
Cyclic AMP-Dependent Protein Kinases/genetics/metabolism
Biotechnology
Muscle contraction
medicine.medical_specialty
animal structures
Ryanodine Receptor Calcium Release Channel/genetics/metabolism
Biology
Mitochondrial Proteins
ddc:616.9802
Muscle Proteins/genetics/*metabolism
Internal medicine
Genetics
medicine
Cold acclimation
Animals
Muscle
Skeletal
Molecular Biology
Thermogenesis/*physiology
Soleus muscle
Shivering/physiology
Acclimatization/*physiology
Skeletal muscle
Ryanodine Receptor Calcium Release Channel
Cyclic AMP-Dependent Protein Kinases
Endocrinology
Calcium
Zdroj: FASEB Journal, Vol. 22, No 11 (2008) pp. 3919-3924
ISSN: 0892-6638
Popis: When acutely exposed to a cold environment, mammals shiver to generate heat. During prolonged cold exposure, shivering is replaced by adaptive adrenergic nonshivering thermogenesis with increased heat production in brown adipose tissue due to activation of uncoupling protein-1 (UCP1). This cold acclimation is associated with chronically increased sympathetic stimulation of skeletal muscle, which may increase the sarcoplasmic reticulum (SR) Ca2+ leak via destabilized ryanodine receptor 1 (RyR1) channel complexes. Here, we use genetically engineered UCP1-deficient (UCP1-KO) mice that rely completely on shivering in the cold. We examine soleus muscle, which participates in shivering, and flexor digitorum brevis (FDB) muscle, a distal and superficial muscle that does not shiver. Soleus muscles of cold-acclimated UCP1-KO mice exhibited severe RyR1 PKA hyperphosphorylation and calstabin1 depletion, as well as markedly decreased SR Ca2+ release and force during contractions. In stark contrast, the RyR1 channel complexes were little affected, and Ca2+ and force were not decreased in FDB muscles of cold-acclimated UCP1-KO mice. These results indicate that activation of UCP1-mediated heat production in brown adipose tissue during cold exposure reduces the necessity for shivering and thus prevents the development of severe dysfunction in shivering muscles. Aydin, J., Shabalina, I. G., Place, N., Reiken, S., Zhang, S.-J., Bellinger, A. M., Nedergaard, J., Cannon, B., Marks, A. R., Bruton, J. D., Westerblad, H. Nonshivering thermogenesis protects against defective calcium handling in muscle.
Databáze: OpenAIRE
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