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
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal secondary targets IgM (Heavy chain)
View all literature mentionsThis unknown targets IgG1
View all literature mentionsThis polyclonal secondary targets IgG2b
View all literature mentionsThis monoclonal targets Myosin Heavy Chain Type IIB
View all literature mentionsThis monoclonal targets Myosin Heavy Chain Type IIA
View all literature mentionsThis unknown targets Mouse Bovine myosin heavy chain slow alpha- and beta-
View all literature mentionsThis unknown targets TNF alpha
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Laminin antibody produced in rabbit
View all literature mentionsThis monoclonal targets Pax7
View all literature mentionsThis monoclonal targets MYOD
View all literature mentionsThis unknown targets Rabbit IgG, whole molecule
View all literature mentionsThis monoclonal targets Bad
View all literature mentionsThis monoclonal targets GSK-3beta (27C10) Rabbit mAb
View all literature mentionsThis monoclonal targets Akt (pan) (C67E7) Rabbit mAb
View all literature mentionsThis monoclonal targets Casp3
View all literature mentionsCell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsThis monoclonal targets Phospho-GSK-3 (Ser9)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis polyclonal secondary targets IgM (Heavy chain)
View all literature mentionsThis polyclonal secondary targets IgM (Heavy chain)
View all literature mentions