Activation of AMPK restored impaired autophagy and inhibited inflammation reaction by up-regulating SIRT1 in acute pancreatitis

Wang, Xiao-Die; Yu, Wancheng; Sun, Yun

doi:10.1016/j.lfs.2021.119435

Cited by 20 publications

(22 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BALB/c mice (n=18, male, 28-35 g; age, 6-8 weeks) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. All mice were maintained under SPF conditions. All procedures performed in this study involving animals were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (34). The animal experiments were approved by the Animal Care and Use Committee of The First Affiliated Hospital of Zhejiang Chinese Medical University (approval no.…”

Section: Reagents Emodin Was Purchased From Beijing Solarbiomentioning

confidence: 99%

Emodin inhibits the progression of acute pancreatitis via regulation of lncRNA TUG1 and exosomal lncRNA TUG1

Wen

Tang

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

Acute pancreatitis (AP) is one of the most frequent gastrointestinal diseases and has no specific treatment. It has been shown that dysfunction of pancreatic acinar cells can lead to AP progression. Emodin is a natural product, which can alleviate the symptoms of AP. However, the mechanism by which emodin regulates the function of pancreatic acinar cells remains unclear. Thus, the present study aimed to investigate the mechanism by which emodin modulates the function of pancreatic acinar cells. To mimic AP in vitro, pancreatic acinar cells were cotreated with caerulein and lipopolysaccharide (LPS). Exosomes were isolated using the ExoQuick precipitation kit. Western blot analysis, Nanosight Tracking analysis and transmission electron microscopy were performed to detect the efficiency of exosome separation. Gene expression was detected by reverse transcription-quantitative PCR. The levels of IL-1β and TNF-α were detected by ELISA. The data indicated that emodin significantly decreased the levels of IL-1β and TNF-α in the supernatant samples derived from AR42J cells cotreated with caerulein and LPS. In addition, emodin significantly promoted the proliferation of AR42J cells cotreated with caerulein and LPS, and inhibited apoptosis, while the effect of emodin was reversed by long non-coding (lnc)RNA taurine upregulated 1 (TUG1) overexpression. The expression level of TUG1 in AR42J cells or exosomes derived from AR42J cells was significantly increased following treatment of the cells with LPS and caerulein, while this effect was notably reversed by emodin treatment. In addition, exosomes derived from caerulein and LPS cotreated AR42J cells inhibited the differentiation and anti-inflammatory function of regulatory T cells, while treatment of the cells with emodin significantly decreased this effect. In conclusion, the data indicated that emodin inhibited the induction of inflammation in AR42J cells by regulating the expression of cellular and exosomal lncRNA. Therefore, emodin may be used as a potential agent for the treatment of AP.

show abstract

Section: Reagents Emodin Was Purchased From Beijing Solarbiomentioning

confidence: 99%

Emodin inhibits the progression of acute pancreatitis via regulation of lncRNA TUG1 and exosomal lncRNA TUG1

Wen

Tang

et al. 2021

Mol Med Rep

View full text Add to dashboard Cite

show abstract

“…The sections were cut with ultrafine slicing machine (Boeckeler, Tucson, AZ, USA), photographed using a transmission electron microscope (Hitachi H-7650, Tokyo, Japan). The swollen mitochondria and autolysosome number was analyzed according to the methods in previous studies ( 22 – 24 ).…”

Section: Methodsmentioning

confidence: 99%

Zinc Oxide Nanoparticle Improves the Intestinal Function of Intrauterine Growth Retardation Finishing Pigs via Regulating Intestinal Morphology, Inflammation, Antioxidant Status and Autophagy

et al. 2022

View full text Add to dashboard Cite

This study was to investigate effects of zinc oxide nanoparticle (Nano-ZnO) on growth, immunity, intestinal morphology and function of intrauterine growth retardation (IUGR) finishing pigs. Six normal birth weight (NBW) and 12 IUGR male piglets were obtained and weaned at 21 d. NBW-weaned piglets fed basal diets (NBW group), IUGR-weaned piglets allocated to two groups fed basal diets (IUGR group) and basal diets further supplemented 600 mg Zn/kg from Nano-ZnO (IUGR+Zn group), respectively. All pigs were slaughtered at 163 d. Results showed: (1) IUGR pigs showed no difference in body weight at 77d and 163d (P > 0.05), while had increased villus height (VH) and villus surface area in jejunum (P < 0.05) and enhanced interleukin-6, TNF-α and NF-κB mRNA expression (P < 0.05) as compared to NBW group; Compared with IUGR group, dietary Nano-ZnO did not affect the body weight (P > 0.05), but increased VH to crypt depth ratio and IgA concentration (P < 0.05) and decreased TNF-α and NF-κB mRNA expression in jejunum (P < 0.05). (2) IUGR increased the number of swollen mitochondria and autolysosomes, and protein expressions of sequestosome-1 (P62) and microtubule-associated protein light chain 3 B/A (LC3B/A) in jejunum as compared to NBW group (P < 0.05); Compared with IUGR group, Nano-ZnO decreased the number of swollen mitochondria and autolysosomes, and P62 and LC3B/A protein expression (P < 0.05). (3) IUGR increased mucosal contents of malondialdehyde and protein carbonyl (PC) and Keap1 protein expression (P < 0.05) as compared to NBW group; Compared with IUGR group, dietary Nano-ZnO increased activities of total antioxidant capacity, catalase, glutathione peroxidase, and glutathione content (P < 0.05), and enhanced nuclear respiratory factor 2 (Nrf2), glutamate-cysteine ligase modifier subunit and glutathione peroxidase 1 mRNA expression, and increased total and nuclear Nrf2 protein expression (P < 0.05), and decreased malondialdehyde and PC content, and Keap1 protein expression (P < 0.05) in jejunum. Results suggested that IUGR pigs showed postnatal catch-up growth and improved intestinal morphology, and dietary Nano-ZnO may further improve intestinal morphology, reduce inflammation, decrease autophagy and alleviate oxidative stress via Nrf2/Keap1 pathway in jejunum of IUGR pigs.

show abstract

“…However, treatment with AMPK activators could attenuate these behavioral and molecular changes in the pathophysiological profile of metabolic dysfunction (Wang et al 2018 ). Various studies have shown that treatment with metformin is effective in neurological diseases, including high MPTP and increased BDNF (Patil et al 2014 , Lu et al 2016 ), Parkinson’s disease (Choi et al 2010 ; Arbeláez-Quintero and Palacios 2017 ; Lu et al 2020 , Paudel et al 2020 ), epilepsy (H S, Paudel et al 2019 , Demaré et al 2021 ; Sanz et al 2021 , Salvati et al 2022 ), traumatic brain injury (Tao et al 2018 ; Taheri et al 2019 ; Fan et al 2020 ; Rahimi et al 2020 ), neuroprotection of the heart (Zhu et al 2018 , Benjanuwattra et al 2020 , Leech et al 2020 ), and preconditioning in ischemic brain injury (Wang et al 2021a , b , c ). Various studies have shown that BDNF can affect the structure of the anal sphincter (Singh and Rattan 2021 , Singh, Singh et al 2021 ).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

“…Indeed, metformin administration in STZ-diabetic rats resulted in improved testosterone, LH and FSH hormones levels (Nasrolahi et al 2013 ). Various studies have shown that treatment with metformin is effective in reproductive system diseases, including female and male reproduction in endocrine pathologies (Lee et al 2019 ; Shpakov 2021 , ul haq Shah, Shrivastava et al 2022 ), endometriosis (Zhao et al 2018 , Mu et al 2020 , Stochino-Loi et al 2021 , Kimber-Trojnar et al 2022 ), polycystic ovary syndrome (Chen et al 2019 ; Fornes et al 2022 , Xu et al 2022 ) and prostate (Sun et al 2018 , Chen, Wang et al 2021a , b , c , Aydın et al 2022 , Morale et al 2022 ).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

“…Furthermore, another investigation revealed that inhibiting the activation of the two pathways of STAT3 and NF-βB by AMPK has been effective in inhibiting the growth of pancreatic tumours (Tan et al 2015 ). In addition, various studies have shown that treatment with metformin is effective in digestive system diseases, including colitis (El-Mahdy et al 2021 , Liu, Liao et al 2021, El-Ghannam et al 2022 ), Pancreatitis (He et al 2021 , Wang et al 2021a , b , c , Wang, Yu et al 2021), Liver Disease (Saeedi Saravi et al 2016 , Pinyopornpanish et al 2021 , Xie, Wang et al 2021a , b , c ) and Gut Microbiota (Lee, Chae et al 2021b , a , Lee, Kim et al 2021, Liu, Liao et al 2021).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

See 1 more Smart Citation

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Hasanvand

2022

Inflammopharmacol

View full text Add to dashboard Cite

Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin’s action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin’s activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells’ proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases. Graphical abstract

show abstract

Activation of AMPK restored impaired autophagy and inhibited inflammation reaction by up-regulating SIRT1 in acute pancreatitis

Cited by 20 publications

References 39 publications

Emodin inhibits the progression of acute pancreatitis via regulation of lncRNA TUG1 and exosomal lncRNA TUG1

Emodin inhibits the progression of acute pancreatitis via regulation of lncRNA TUG1 and exosomal lncRNA TUG1

Zinc Oxide Nanoparticle Improves the Intestinal Function of Intrauterine Growth Retardation Finishing Pigs via Regulating Intestinal Morphology, Inflammation, Antioxidant Status and Autophagy

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Contact Info

Product

Resources

About