TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine.

TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Research Abstract Details 

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TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Abstract Text:

Charu Dogra,Harish Changotra,Nia Wedhas,Xuezhong Qin,Jon E Wergedal,Ashok Kumar,

TWEAK cytokine has been implicated in several biological responses including inflammation, angiogenesis, and osteoclastogenesis. We have investigated the role of TWEAK in regulating skeletal muscle mass. Addition of soluble TWEAK protein to cultured myotubes reduced the mean myotube diameter and enhanced the degradation of specific muscle proteins such as CK and MyHCf. The effect of TWEAK on degradation of MyHCf was stronger than its structural homologue, TNF-alpha. TWEAK increased the ubiquitination of MyHCf and the transcript levels of atrogin-1 and MuRF1 ubiquitin ligases. TWEAK inhibited phosphorylation of Akt kinase and its downstream targets GSK-3beta, FOXO1, mTOR, and p70S6K. Furthermore, TWEAK increased the activation of NF-kappaB transcription factor in myotubes. Adenoviral-mediated overexpression of IkappaB alpha deltaN (a degradation-resistant mutant of NF-kappaB inhibitory protein IkappaB alpha) in myotubes blocked the TWEAK-induced degradation of MyHCf. Chronic administration of TWEAK in mice resulted in reduced body and skeletal muscle weight with an associated increase in the activity of ubiquitin-proteasome system and NF-kappaB. Finally, muscle-specific transgenic overexpression of TWEAK decreased the body and skeletal muscle weight in mice. Collectively, our data suggest that TWEAK induces skeletal muscle atrophy through inhibition of the PI3K/Akt signaling pathway and activation of the ubiquitin-proteasome and NF-kappaB systems.

TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Publishing Authors By Initials

C Dogra,H Changotra,N Wedhas,X Qin,JE Wergedal,A Kumar,

For similar proteins: ubiquitins: ubiquitin research abstracts see: proteins: ubiquitins: ubiquitin research

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TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The FASEB journal : official publication of the Fe

VOLUME: 21

Page Numbers: 1857-69

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 21

MONTH: 02

YEAR: 2007

TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8804484

TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Keywords Mesh Terms:

KEYWORDS: Ubiquitin

MESH TERMS: metabolism

Chemical & Substance for Abstract: TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. Information

Substance Name: Proteasome Endopeptidase Complex

Registry Number: EC 3.4.25.1

Grant and Affiliation Information for TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine.

AFFILIATION: Musculoskeletal Disease Center, Jerry L. Pettis Memorial Veterans Administration Medical Center, Loma Linda, CA 92357, USA.

Country: United States

AGENCY: United States NIA

GRANT: R01 AG129623

ACRONYM: AG

MEDLINETA: FASEB J

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