Src homology and collagen homology (Shc) mediates autophagy induced by troglitazone in PAE cells

Abstract:

Abstract:［Objective］ We investigated the mechanism of Src homology and collagen homology (Shc) in autophagy caused by troglitazone (TZ).［Methods］To reveal the regulatory role of p52Shc in autophagy，we used confocal microscopy and immunoblotting to examine autophagy induced by TZ. Then we used small RNA interference (siRNA) to deplete Shc and plasmids transfection to overexpress wtShc as well as 3mShc in PAE cells. Finally，we reached conclusion by detecting autophagic status following the deprivation of UNC-51-like kinase -1(Ulk1) by siRNA.［Results］We found that the deprivation of Shc showed to enhance autophagy，whereas p52Shc over expression suppressed TZ-depended autophagy concurring with an attenuated AMP-activated protein kinase (AMPK) and Ulk1 signaling. Besides，it demonstrated that p52Shc tyrosine sites of 239，240 and 317 implemented a critical role in the process.［Conclusion］ Collectively，Shc adaptor protein was involved in TZ-inducing autophagy likely via affecting AMPK and Ulk1 signaling．