How to build muscle mass with four and a half LIM domains 1
A former Sydney skin cancer doctor who may have jeopardised the health of thousands of his former patients is apparently planning to appeal against his deregistration. Following a Health Department investigation which revealed serious concerns about the treatment of some of David Lindsay’s patients received at the Mid-City Skin Cancer Centre in George Street, in
Full Post: Deregistered cancer doctor in denial about risking 6,770 lives
Cowling et al. report how to build muscle mass with FHL1. The protein partners with and activates the transcription factor, NFATc1.
Encouraging this partnership might provide a possible treatment for muscle wasting disorders. The article will appear in the December 15, 2008 issue of The Journal of Cell Biology (JCB).
Mutations in ‘Four and a half LIM domains 1′ (FHL1), a human gene, are present in several myopathies, including reducing-body myopathy (RBM), but until now, both the molecular mechanisms causing the disease, and the regular function of FHL1 in healthy tissue, remained unknown.
To address this, Cowling et al. overexpressed FHL1 in both transgenic mice and cultured myoblasts. The mice developed skeletal muscle hypertrophy, and showed increased strength and endurance. Overexpression in myoblasts also increased cell fusion, resulting in hypertrophic myotubes. These phenotypes are similar to those caused by the calcineurin/NFAT pathway and, indeed, inhibiting calcineurin blocked the effects of FHL1 overexpression in vitro. The authors showed that FHL1 binds to and enhances the transcriptional activity of NFATc1 in vitro and in vivo.
So what goes wrong when FHL1 is mutated? In RBM, mutant FHL1 accumulates in cytoplasmic aggregates called reducing bodies, probably as a result of misfolding. When these mutants were expressed in cultured myoblasts, they also aggregated, and did not induce hypertrophy. Cowling and colleagues found that NFATc1 was sequestered to the aggregates, and was therefore unable to activate its target genes.
Individuals who have persistent high blood pressure are at increased risks of a number of serious medical conditions, including heart failure. One of the factors that contributes to such heart failure is thickening of the muscle wall of the heart. Such thickening (known as hypertrophy) is a compensatory response of the heart to the high
Full Post: Molecular insight into how a heart failure drug in clinical trials works
Johns Hopkins and other researchers report what is believed to be the first direct evidence in lab animals that the erectile dysfunction drug sildenafil amplifies the effects of a heart-protective protein. The team’s findings, to be published in the Journal of Clinical Investigation online Jan. 5, helps explain why sildenafil, more widely known as Viagra,
Full Post: Viagra may help protect heart from high blood pressure damage
Researchers at Children’s Hospital of Pittsburgh of UPMC have been able to effectively repair damaged heart muscle in an animal model using a novel population of stem cells they discovered that is derived from human skeletal muscle tissue. The research team - led by Johnny Huard, PhD - transplanted stem cells purified from human muscle-derived
Full Post: Researchers repair injured heart muscle with novel stem cells
The first demonstration that a single adult stem cell can self-renew in a mammal was reported at the American Society for Cell Biology (ASCB) 48th Annual Meeting, Dec. 13-17, 2008 in San Francisco. The transplanted adult stem cell and its differentiated descendants restored lost function to mice with hind limb muscle tissue damage. The adult
Full Post: Single adult stem cell can self-renew in a mammal
Scientists call it the “French paradox” - a society that, despite consuming food high in cholesterol and saturated fats, has long had low death rates from heart disease. Research has suggested it is the red wine consumed with all that fatty food that may be beneficial - and not only for cardiovascular health but in
Full Post: Researchers discover how red wine may reduce Alzheimer’s