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Angiotensin-II-induced Muscle Wasting is Mediated by 25-Hydroxycholesterol via GSK3β Signaling Pathway.

EBioMedicine | 2017

While angiotensin II (ang II) has been implicated in the pathogenesis of cardiac cachexia (CC), the molecules that mediate ang II's wasting effect have not been identified. It is known TNF-α level is increased in patients with CC, and TNF-α release is triggered by ang II. We therefore hypothesized that ang II induced muscle wasting is mediated by TNF-α. Ang II infusion led to skeletal muscle wasting in wild type (WT) but not in TNF alpha type 1 receptor knockout (TNFR1KO) mice, suggesting that ang II induced muscle loss is mediated by TNF-α through its type 1 receptor. Microarray analysis identified cholesterol 25-hydroxylase (Ch25h) as the down stream target of TNF-α. Intraperitoneal injection of 25-hydroxycholesterol (25-OHC), the product of Ch25h, resulted in muscle loss in C57BL/6 mice, accompanied by increased expression of atrogin-1, MuRF1 and suppression of IGF-1/Akt signaling pathway. The identification of 25-OHC as an inducer of muscle wasting has implications for the development of specific treatment strategies in preventing muscle loss.

Pubmed ID: 28161398 RIS Download

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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Phospho-GSK-3 (Ser9) (D85E12) XP Rabbit mAb (antibody)

RRID:AB_10013750

This monoclonal targets Phospho-GSK-3 (Ser9)

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Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (antibody)

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This monoclonal targets Phospho-Akt (Ser473)

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Bad (11E3) (antibody)

RRID:AB_10695002

This monoclonal targets BAD

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Mouse Anti-Bovine myosin heavy chain, slow, alpha- and beta- Antibody, Unconjugated (antibody)

RRID:AB_2235587

This unknown targets Mouse Bovine myosin heavy chain slow alpha- and beta-

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Anti-Laminin antibody produced in rabbit (antibody)

RRID:AB_477163

This polyclonal targets Laminin antibody produced in rabbit

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myogenin (antibody)

RRID:AB_2146602

This monoclonal targets Myog

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GSK-3beta (27C10) Rabbit mAb (antibody)

RRID:AB_490890

This monoclonal targets GSK-3beta (27C10) Rabbit mAb

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Akt (pan) (C67E7) Rabbit mAb (antibody)

RRID:AB_915783

This monoclonal targets Akt (pan) (C67E7) Rabbit mAb

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C2C12 (cell line)

RRID:CVCL_0188

Cell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)

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Phospho-GSK-3 (Ser9) (D85E12) XP Rabbit mAb (antibody)

RRID:AB_10013750

This monoclonal targets Phospho-GSK-3 (Ser9)

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Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (antibody)

RRID:AB_2315049

This monoclonal targets Phospho-Akt (Ser473)

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