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

Abstract 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 (Na HS ) 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 Na HS 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 ( ULK 1). 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.