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Myostatin Deficiency But Not Anti-Myostatin Blockade Induces Marked Proteomic Changes in Mouse Skeletal Muscle

ABSTRACT: Recent studies have reported the deleterious physiological and metabolic changes in Mstn-/- mice including impaired force generation and susceptibility to contraction-induced injury. Such observations have raised the concerns about the functional quality of the increased muscle resulting from therapeutic blockade of Mstn. Here we provide proteomic evidence to demonstrate that therapeutic Mstn inhibition has minimal effects on muscle proteome composition whereas the genetic ablation of Mstn induces marked changes. Furthermore, this study also represents the first proteomic analysis of the pharmacological blockage of the Mstn/activin receptor pathway being actively pursued as a potential therapy for multiple muscle wasting disorders.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Gastrocnemius

SUBMITTER: Robert Salzler

LAB HEAD: Xunbao Duan

PROVIDER: PXD003747 | Pride | 2016-05-31

REPOSITORIES: Pride

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Myostatin deficiency but not anti-myostatin blockade induces marked proteomic changes in mouse skeletal muscle.

Salzler Robert R RR Shah Darshit D Doré Anthony A Bauerlein Roy R Miloscio Lawrence L Latres Esther E Papadopoulos Nicholas J NJ Olson William C WC MacDonald Douglas D Duan Xunbao X

Proteomics 20160701 14

Pharmacologic blockade of the myostatin (Mstn)/activin receptor pathway is being pursued as a potential therapy for several muscle wasting disorders. The functional benefits of blocking this pathway are under investigation, in particular given the findings that greater muscle hypertrophy results from Mstn deficiency arising from genetic ablation compared to post-developmental Mstn blockade. Using high-resolution MS coupled with SILAC mouse technology, we quantitated the relative proteomic change ...[more]

PMID: 27214824

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