2482-PUB: Circadian Clock Regulates Fuel Metabolism in Skeletal Muscles

Insulin-like growth factor (IGF) signaling plays an important role in cell growth and proliferation and is implicated in regulation of cancer, metabolism, and aging. Here we report that IGF-1 level in blood and IGF-1 signaling demonstrates circadian rhythms. Circadian control occurs through cryptochromes (CRYs)—transcriptional repressors and components of the circadian clock. IGF-1 rhythms are disrupted in Cry-deficient mice, and IGF-1 level is reduced by 80% in these mice, which leads to reduced IGF signaling. In agreement, Cry-deficient mice have reduced body (∼30% reduction) and organ size. Down-regulation of IGF-1 upon Cry deficiency correlates with reduced Igf-1 mRNA expression in the liver and skeletal muscles. Igf-1 transcription is regulated through growth hormone–induced, JAK2 kinase–mediated phosphorylation of transcriptional factor STAT5B. The phosphorylation of STAT5B on the JAK2-dependent Y699 site is significantly reduced in the liver and skeletal muscles of Cry-deficient mice. At the same time, phosphorylation of JAK2 kinase was not reduced upon Cry deficiency, which places CRY activity downstream from JAK2. Thus CRYs link the circadian clock and JAK-STAT signaling through control of STAT5B phosphorylation, which provides the mechanism for circadian rhythms in IGF signaling in vivo.

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Different fuel regulation in two types of myofiber results in different antioxidant strategies in Daurian ground squirrels (Spermophilus dauricus) during hibernation

Journal of Experimental Biology ◽

10.1242/jeb.231639 ◽

2020 ◽

pp. jeb.231639

Author(s):

Xu Shen-Hui ◽

Wei-Wei Fu ◽

Jie Zhang ◽

Hui-Ping Wang ◽

Kai Dang ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Capacity ◽

Skeletal Muscles ◽

Extensor Digitorum Longus ◽

Antioxidant Defense ◽

Ground Squirrels ◽

Strategy Formation ◽

Fuel Metabolism ◽

Hypoxic Conditions ◽

Edl Muscle

We previously showed that different skeletal muscles in Daurian ground squirrels (Spermophilus dauricus) possess different antioxidant strategies during hibernation; however, the reason for these varied strategies remains unclear. To clarify this issue, we studied REDD1, FOXO4, PGC-1α, FOXO1, and atrogin-1 proteins to determine the potential cause of the different antioxidant strategies in Daurian ground squirrels during hibernation, and to clarify whether different strategies affect atrophy-related signals. Results showed that the soleus (SOL) muscle experienced intracellular hypoxia during interbout arousal, but no oxidative stress. This may be due to increased PGC-1α expression enhancing antioxidant capacity in the SOL under hypoxic conditions. Extensor digitorum longus (EDL) muscle showed no change in oxidative stress, hypoxia, or antioxidant capacity during hibernation. The FOXO1 and PGC-1α results strongly suggested differentially regulated fuel metabolism in the SOL and EDL muscles during hibernation, i.e., enhanced lipid oxidation and maintained anaerobic glycolysis, respectively. Atrogin-1 expression did not increase during hibernation in either the SOL or EDL, indicating that protein synthesis was not inhibited by atrogin-1. Thus, our results suggest that different fuel regulation may be one mechanism related to antioxidant defense strategy formation in different kinds of skeletal muscle fibers of Daurian ground squirrels during hibernation.

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Decision letter for "The SNARE Regulator Complexin3 is a Target of the Cone Circadian Clock"

10.1002/cne.25004/v3/decision1 ◽

2020 ◽

Keyword(s):

Circadian Clock

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Review for "The SNARE Regulator Complexin3 is a Target of the Cone Circadian Clock"

10.1002/cne.25004/v2/review1 ◽

2020 ◽

Author(s):

Gianluca Tosini

Keyword(s):

Circadian Clock

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Distribution of c-protein isoforms in sarcomeres of developing chick skeletal muscle

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010010319x ◽

1988 ◽

Vol 46 ◽

pp. 226-227

Author(s):

D. A. Fischman ◽

J. E. Dennis ◽

T. Obinata ◽

H. Takano-Ohmuro

Keyword(s):

Skeletal Muscles ◽

Thick Filament ◽

Protein Isoforms ◽

Actin Binding ◽

Striated Muscles ◽

C Protein ◽

Sarcomeric Protein ◽

Thick Filaments ◽

Cross Bridges ◽

Bridge Bearing

C-protein is a 150 kDa protein found within the A bands of all vertebrate cross-striated muscles. By immunoelectron microscopy, it has been demonstrated that C-protein is distributed along a series of 7-9 transverse stripes in the medial, cross-bridge bearing zone of each A band. This zone is now termed the C-zone of the sarcomere. Interest in this protein has been sparked by its striking distribution in the sarcomere: the transverse repeat between C-protein stripes is 43 nm, almost exactly 3 times the 14.3 nm axial repeat of myosin cross-bridges along the thick filaments. The precise packing of C-protein in the thick filament is still unknown. It is the only sarcomeric protein which binds to both myosin and actin, and the actin-binding is Ca-sensitive. In cardiac and slow, but not fast, skeletal muscles C-protein is phosphorylated. Amino acid composition suggests a protein of little or no αhelical content. Variant forms (isoforms) of C-protein have been identified in cardiac, slow and embryonic muscles.

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The effect of ionophore A23178 on the α-actinin crosslinks in the z-band of frog skeletal muscle: An EM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142396 ◽

1986 ◽

Vol 44 ◽

pp. 154-155

Author(s):

F.T. Llados ◽

V. Krlho ◽

G.D. Pappas

Keyword(s):

Muscle Damage ◽

Transmitter Release ◽

Skeletal Muscles ◽

Calcium Uptake ◽

Muscle Membrane ◽

Frog Skeletal Muscle ◽

Ach Release ◽

Sustained Action ◽

Calcium Deposits ◽

Intense Stimulation

It Is known that Ca++ enters the muscle fiber at the junctional area during the action of the neurotransmitter, acetylcholine (ACh). Pappas and Rose demonstrated that following Intense stimulation, calcium deposits are found In the postsynaptic muscle membrane, Indicating the existence of calcium uptake In the postsynaptic area following ACh release. In addition to this calcium uptake, when mammal Ian skeletal muscles are exposed to a sustained action of the neurotransmitter, muscle damage develops. These same effects, l.e., Increased transmitter release, calcium uptake and finally muscle damage, can be obtained by Incubating the muscle with lonophore A23178.

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