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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 297/2/E392    most recent 90529.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Ramamoorthy, S. Articles by Buck, M. PubMed PubMed Citation Articles by Ramamoorthy, S. Articles by Buck, M.

Decreased Jun-D and myogenin expression in muscle wasting of human cachexia

¹Department of Surgery, ²Department of Medicine, ³Moores Cancer Center, ⁴General Clinical Research Center, and ⁵Biostatistics and Bioinformatics, University of California San Diego; and ⁶Veterans Affairs Healthcare System, San Diego, California

Submitted 22 June 2008 ; accepted in final form 17 May 2009

Muscle wasting is a critical feature of patients afflicted by acquired immune deficiency syndrome (AIDS), cancer, or chronic inflammatory diseases. In a mouse model of muscle wasting, TNF- induces oxidative stress and nitric oxide synthase-2 (NOS2) and decreases myogenin, Jun-D, and creatinine kinase muscle isoform (CKM) expression. Here, we studied 12 patients with muscle wasting due to cancer (N = 10) or AIDS (N = 2) and 4 control subjects. We show that in skeletal muscle of cachectic patients there is 1) increased expression and activity of the TNF- signaling, including TNF- mRNA, activation of TNFR1, and TNF--associated to TNFR1; 2) increased oxidative stress, as determined by the presence of malondialdehyde-lysine adducts; 3) increased NOS2 mRNA and protein; 4) decreased expression of Jun-D, myogenin, myosin, and CKM mRNA and protein; 5) impaired CKM-E box binding activities, associated with decreased Jun-D/myogenin activities; and 6) oxidative modification and ubiquitination of Jun-D. These studies show that these molecular pathways are modulated in association with muscle wasting in patients with cancer or AIDS, and whether or not they cause muscle wasting remains to be determined.

muscle atrophy; creatinine kinase; nitric oxide synthase-2; Ref-1

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