Hydrogen sulphide exacerbates acute pancreatitis by over‐activating autophagy via AMPK/mTOR pathway

Previously, we have shown that hydrogen sulphide (H(2)S) might be pro‐inflammatory during acute pancreatitis (AP) through inhibiting apoptosis and subsequently favouring a predominance of necrosis over apoptosis. In this study, we sought to investigate the detrimental effects of H(2)S during AP specifically with regard to its regulation on the impaired autophagy. The incubated levels of H(2)S were artificially intervened by an administration of sodium hydrosulphide (NaHS) or DL‐propargylglycine (PAG) after AP induction. Accumulation of autophagic vacuoles and pre‐mature activation of trypsinogen within acini, which indicate the impairment of autophagy during AP, were both exacerbated by treatment with NaHS but attenuated by treatment with PAG. The regulation that H(2)S exerted on the impaired autophagy during AP was further attributed to over‐activation of autophagy rather than hampered autophagosome–lysosome fusion. To elucidate the molecular mechanism that underlies H(2)S‐mediated over‐activation of autophagy during AP, we evaluated phosphorylations of AMP‐activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR). Furthermore, Compound C (CC) was introduced to determine the involvement of mTOR signalling by evaluating phosphorylations of downstream effecters including p70 S6 kinase (P70S6k) and UNC‐51‐Like kinase 1 (ULK1). Our findings suggested that H(2)S exacerbated taurocholate‐induced AP by over‐activating autophagy via activation of AMPK and subsequently, inhibition of mTOR. Thus, an active suppression of H(2)S to restore over‐activated autophagy might be a promising therapeutic approach against AP‐related injuries.