Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis

Hu, Yangyang; Zhou, Chunhua; Dou, Wen-Huan; Tang, Wen; Hu, Chuang-Ying; Hu, Duanmin; Feng, Hui; Wang, Jian-Zong; Ming-hui, Qian; Cheng, Guangfeng; Wang, Shaofeng

doi:10.1016/j.pan.2015.06.004

Cited by 12 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Coincidently, the present study demonstrated that EGCG inhibited the over-activation of autophagy and promoted autophagosome clearance, accompanied by the upregulation of both p-Akt and p-mTOR. Since the activation of mTOR signaling is known to inhibit autophagic activity and improve autophagic flux (39,40), our data suggest that EGCG attenuates I/R-induced excessive autophagy and restores the autophagic flux through the PI3K/Akt/mTOR pathway.…”

Section: Discussionmentioning

confidence: 74%

Epigallocatechin gallate exerts protective effects against myocardial ischemia/reperfusion injury through the PI3K/Akt pathway-mediated inhibition of apoptosis and the restoration of the autophagic flux

Xuan

Jian

2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Epigallocatechin gallate (EGCG), a polyphenol derived from green tea, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. In this study, the cardioprotective effects of EGCG on myocardial ischemia/reperfusion (I/R) injury in rats and the underlying mechanisms were investigated. A rat model of I/R injury was established by ligating the left anterior descending coronary artery for 30 min, followed by reperfusion for 2 h. The levels of I/R-induced creatine kinase-MB (CK-MB) and the release of lactate dehydrogenase (LDH), as well as the infarct size, cardiomyocyte apoptosis and cardiac functional impairment were examined and compared. Western blot analysis was carried out to elucidate the potential molecular mechanisms of action of EGCG. The results revealed that EGCG post-conditioning significantly decreased the levels of CK-MB and the release of LDH, reduced the myocardial infarct size, decreased the apoptotic rate and partially preserved heart function. Furthermore, EGCG decreased the expression of cleaved caspase-3 concomitantly with the upregulation of PI3K, and the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). It also inhibited I/R-induced overautophagy and promoted the clearance of autophagosomes, as evidenced by a decrease in the ratio of microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I, the downregulation of Beclin1, Atg5 and p62, and the upregulation of active cathepsin D. Additionally, we observed an increase in the phosphorylation levels of the mammalian target of rapamycin (mTOR) following treatment with EGCG. Taken together, the findings of this study demonstrate that, EGCG post-conditioning alleviates myocardial I/R injury by inhibiting apoptosis and restoring the autophagic flux, which is associated with several targets of the PI3K/Akt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 74%

Epigallocatechin gallate exerts protective effects against myocardial ischemia/reperfusion injury through the PI3K/Akt pathway-mediated inhibition of apoptosis and the restoration of the autophagic flux

Xuan

Jian

2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

“…Obviously, it will be important to conduct new studies in other systems to begin to support that assertion; however, we can at this point re-examine the extant literature to determine whether roles for lysosomes/autophagy and/or mTORC1 in the process of cellular reprogramming to a regenerative state have previously been described. One such previous study, using a different injury protocol, with the endpoint to determine the role of mTORC1 and autophagy in severity of pancreatitis, similarly showed a pattern of early autodegradation followed by mTORC1 activation (Hu et al, 2015). The authors also found that rapamycin worsened severity of pancreatitis.…”

Section: Discussionmentioning

confidence: 84%

“…One such previous study, using a different injury protocol, with the endpoint to determine the role of mTORC1 and autophagy in severity of pancreatitis, similarly showed a pattern of early autodegradation followed by mTORC1 activation (Hu et al, 2015). Obviously, it will be important to conduct new studies in other systems to begin to support that assertion; however, we can at this point re-examine the extant literature to determine whether roles for lysosomes/autophagy and/or mTORC1 in the process of cellular reprogramming to a regenerative state have previously been described.…”

Section: Discussionmentioning

confidence: 87%

Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

et al. 2018

View full text Add to dashboard Cite

In 1900, Adami speculated that a sequence of context-independent energetic and structural changes governed the reversion of differentiated cells to a proliferative, regenerative state. Accordingly, we show here that differentiated cells in diverse organs become proliferative via a shared program. Metaplasia-inducing injury caused both gastric chief and pancreatic acinar cells to decrease mTORC1 activity and massively upregulate lysosomes/autophagosomes; then increase damage associated metaplastic genes such as ; and finally reactivate mTORC1 and re-enter the cell cycle. Blocking mTORC1 permitted autophagy and metaplastic gene induction but blocked cell cycle re-entry at S-phase. In kidney and liver regeneration and in human gastric metaplasia, mTORC1 also correlated with proliferation. In lysosome-defective mice, both metaplasia-associated gene expression changes and mTORC1-mediated proliferation were deficient in pancreas and stomach. Our findings indicate differentiated cells become proliferative using a sequential program with intervening checkpoints: (i) differentiated cell structure degradation; (ii) metaplasia- or progenitor-associated gene induction; (iii) cell cycle re-entry. We propose this program, which we term "paligenosis", is a fundamental process, like apoptosis, available to differentiated cells to fuel regeneration following injury.

show abstract

“…Sirt1 inhibits apoptosis and inflammation via deacetylating these proteins and thereby modulating their activities, which may also contribute to the protective effect of resveratrol on ANP. Mammalian target of rapamycin (mTOR), an important target of SIRT1, inhibits autophagy and has been implicated in the development of pancreatitis (35,36). SIRT1 influences different pathophysiological processes including metabolism, cell apoptosis and aging by downregulating mTOR (37–39).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol protects against L-arginine-induced acute necrotizing pancreatitis in mice by enhancing SIRT1-mediated deacetylation of p53 and heat shock factor 1

Wang

Zhang

Liu

et al. 2017

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Acute necrotizing pancreatitis (ANP) is a common severe critical illness with a high mortality rate. Resveratrol, a polyphenol compound derived from various plants such as grape skin, peanut, berry and veratrum, exhibits multiple biological activities, especially potent anti-inflammatory activity, but its effect on ANP has not yet been fully elucidated. The present study aimed to investigate the effects of resveratrol on L-arginine-induced ANP and the possible mechanisms. A mouse model of ANP was established by 2 hourly intraperitoneal injections of 8% L-arginine (4 g/kg). Then the mice were treated by intragastric administration of resveratrol (80 mg/kg) every 12 h immediately after the second injection of L-arginine. Mice with ANP showed increased apoptosis of pancreatic acinar cells, pancreatic myeloperoxidase activity, serum lactate dehydrogenase activity, amylase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) levels as well as decreased serum IL-10 level, pancreatic expression of heat shock factor 1 (HSF1), sirtuin 1 (SIRT1) and p53, but the ratio of acetylated HSF1 and p53 was markedly increased. Resveratrol enhanced the survival rate of mice with ANP from 47.8 to 71.4% and obviously restored the changes in mice with ANP as mentioned above. Additionally, interactions between SIRT1 and p53 and between SIRT1 and HSF1 in the pancreas of the mice were confirmed by co-immunoprecipitation. These data suggest that resveratrol protects against L-arginine-induced ANP, which may be related to the enhancement of SIRT1-mediated deacetylation of p53 and HSF1.

show abstract

Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis

Cited by 12 publications

References 53 publications

Epigallocatechin gallate exerts protective effects against myocardial ischemia/reperfusion injury through the PI3K/Akt pathway-mediated inhibition of apoptosis and the restoration of the autophagic flux

Epigallocatechin gallate exerts protective effects against myocardial ischemia/reperfusion injury through the PI3K/Akt pathway-mediated inhibition of apoptosis and the restoration of the autophagic flux

Regenerative proliferation of differentiated cells by mTORC 1‐dependent paligenosis

Resveratrol protects against L-arginine-induced acute necrotizing pancreatitis in mice by enhancing SIRT1-mediated deacetylation of p53 and heat shock factor 1

Contact Info

Product

Resources

About