Crossroads of cytokine signaling--the chase to stop muscle cachexia.
There is no universal approach to stop muscle cachexia in a number of life-threatening diseases. Accordingly, it is uncertain why the body mass is so critical to keep alive patients with cancer, congestive heart failure (CHF), AIDS or sepsis. At present, it is widely believed that excess muscle wasting diminishes lean body mass to the risky level accompanied by anorexia, anemia, lipolysis, acute phase response and insulin resistance. If missed and/or untreated muscle cachexia inevitably leads to death due to cardiac and respiratory failure (almost one-third of all cancer deaths). This complex metabolic disorder is suited by the elevated levels of inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1-beta, IL-6, IL-2) and low levels of anti-inflammatory/ other cytokines (IL-15, leptin). Concurrently, tissue sensitivity to insulin is considerably reduced. Recent findings indicate that entirely few muscle-specific genes (i.e. MyoD and myosin heavy chain, MyHC) and their products must be targeted to initiate muscle wasting. Muscle atrophy occurs at different levels, starting from repressed gene expression and ended with accelerated protein degradation. Muscle growth (myogenesis) is severely compromised and disruption of sarcomere architecture heralds the proteolysis of contractile apparatus. This review aims to synthesize our present knowledge of intracellular mechanisms and molecular regulation of muscle cachexia with respect to cytokine signaling.
Pajak
B
B
Department of Cell Ultrastructure, Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Orzechowska
S
S
Pijet
B
B
Pijet
M
M
Pogorzelska
A
A
Gajkowska
B
B
Orzechowski
A
A
D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D024510:Muscle Development; D009133:Muscular Atrophy / Q000209:etiology; D015398:Signal Transduction
D016207:Cytokines; D018836:Inflammation Mediators