41 research outputs found

    Signaling through the TRAIL receptor DR5/FADD pathway plays a role in the apoptosis associated with skeletal myoblast differentiation

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    Apoptosis rather than differentiation is a physiological process during myogenesis and muscle regeneration. When cultured myoblasts were induced to differentiate, we detected an increase in caspase 8 activity. Pharmacological inhibition of caspase 8 activity decreased apoptosis. Expression of a dominant-negative mutant of the adapter protein FADD also abrogated apoptosis, implicating a death ligand pathway. Treatment with TRAIL, but not Fas, induced apoptosis in these myoblasts. Accordingly, treatment with a soluble TRAIL decoy receptor or expression of a dominant-negative mutant of the TRAIL receptor DR5 abrogated apoptosis. While TRAIL expression levels remained unaltered in apoptotic myoblasts, DR5 expression levels increased. Finally, we also detected a reduction in FLIP, a death-receptor effector protein and caspase 8 competitive inhibitor, to undetectable levels in apoptotic myoblasts. Thus, our data demonstrate an important role for the TRAIL/DR5/FADD/caspase 8 pathway in the apoptosis associated with skeletal myoblast differentiation. Identifying the functional apoptotic pathways in skeletal myoblasts may prove useful in minimizing the myoblast apoptosis that contributes pathologically to a variety of diseases and in minimizing the apoptosis of transplanted myoblasts to treat these and other disease states

    Investigating The Inhibition Of 5-LO Enzyme By Main Cannabinoids Contained In Cannabis Sativa And Seized Resin Cannabis By Using Molecular Modeling

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    Therapeutic cannabis is a subject which many researchers are very interested in all over the world. The effect of main compound of Cannabis is investigated to treat many diseases. Arachidonate 5-lypoxygenase (5-LO) is implicated in cancer progression, inflammation, tissue damage and other sickness. Commonly to inhibit 5-LO enzyme a famous drug Zileuton is used. In our work we compare inhibition of 5-LO by main compounds of cannabis using tools such as molecular mechanics, molecular dynamics and molecular docking by using MOE software (Molecular Operating Environment) [1]. Obtained results show that main cannabinoids inhibit 5- LO better than Zileuton
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