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

Abstract

Previously, we have shown that hydrogen sulphide (H2S) 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 H2S during AP specifically with regard to its regulation on the impaired autophagy. The incubated levels of H2S 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 H2S 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 H2S‐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 H2S exacerbated taurocholate‐induced AP by over‐activating autophagy via activation of AMPK and subsequently, inhibition of mTOR. Thus, an active suppression of H2S to restore over‐activated autophagy might be a promising therapeutic approach against AP‐related injuries.

<p>Baohuoside I Inhibits the Proliferation of Pancreatic Cancer Cells via mTOR/S6K1-Caspases/Bcl2/Bax Apoptotic Signaling</p>

“…25 The core energy regulatory members in cancer cells include AMPK (a low energy sensor activated by low glucose or low ATP) and mTOR (a high-energy sensor activated by high glucose or high ATP). 26,27 In the present study, Baohuoside I activated the phosphorylation of AMPK and inhibited phosphorylation of mTOR and its downstream target S6K1 ( Figure 6). The balance between AMPK and mTOR maintains intracellular ATP metabolism and the uneven activation of either of these pathways results in the initiation of apoptosis.…”

H2S attenuates acute lung inflammation induced by administration of lipopolysaccharide in adult male rats

“…ALI+NaHS group, rats were treated with NaHS at a dose level of 10 mg/kg body weight i.p. (Tong et al 2016), 1 h after induction of ALI (Ji et al 2016); IV. ALI+PAG group, where each rat was i.p.…”

HYAL‐1‐induced autophagy facilitates pancreatic fistula for patients who underwent pancreaticoduodenectomy

“…n = 6; Bar = 50 μm through AMPK/mTOR pathway in acute pancreatitis. 19 We also mentioned that RB1CC1-induced autophagy promotes pancreatic fibrosis and CP progression. 21 But there is no report to discuss the possible mechanism between HYAL-1 and autophagy.…”

“…The serum and ascites levels of amylase and lipase were measured with an autobiochemical analyzer (Toshiba, Tokyo, Japan) as described previously. 19…”