Ginger extract controls mTOR-SREBP1-ER stress-mitochondria dysfunction through AMPK activation in obesity model

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) have been used as important cell-based tools for clinical applications. Oxidative stress-induced apoptosis causes a low survival rate after transplantation, and the underlying mechanisms remain unknown. The endoplasmic reticulum (ER) and mitochondria are vital organelles regulated by adenosine monophosphate (AMP)-activated protein kinase (AMPK), especially during oxidative stress injury. Melatonin exerts an antioxidant effect by scavenging free radicals. Here, we aimed to explore whether cytoprotective melatonin relieves ER stress-mediated mitochondrial dysfunction through AMPK in BMSCs after oxidative stress injury. Methods Mouse BMSCs were isolated and exposed to H2O2 in the absence or presence of melatonin. Thereafter, cell damage, oxidative stress levels, mitochondrial function, AMPK activity, ER stress-related proteins, and apoptotic markers were measured. Additionally, the involvement of AMPK and ER stress in the melatonin-mediated protection of BMSCs against H2O2-induced injury was investigated using pharmacologic agonists and inhibitors. Results Melatonin improved cell survival and restored mitochondrial function. Moreover, melatonin intimately regulated the phosphorylation of AMPK and molecules associated with ER stress pathways. AMPK activation and ER stress inhibition following melatonin administration improved the mitochondrial membrane potential (MMP), reduced mitochondria-initiated oxidative damage, and ultimately suppressed apoptotic signaling pathways in BMSCs. Cotreatment with N-acetyl-l-cysteine (NAC) significantly enhanced the antioxidant effect of melatonin. Importantly, pharmacological AMPK activation/ER stress inhibition promoted melatonin-induced cytoprotection, while pharmacological AMPK inactivation/ER stress induction conferred resistance to the effect of melatonin against H2O2 insult. Conclusions Our data also reveal a new, potentially therapeutic mechanism by which melatonin protects BMSCs from oxidative stress-mediated mitochondrial apoptosis, possibly by regulating the AMPK-ER stress pathway.

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Ginger Extract Ameliorates Obesity and Inflammation via Regulating MicroRNA-21/132 Expression and AMPK Activation in White Adipose Tissue

Nutrients ◽

10.3390/nu10111567 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1567 ◽

Cited By ~ 13

Author(s):

Seunghae Kim ◽

Mak-Soon Lee ◽

Sunyoon Jung ◽

Hye-Yeon Son ◽

Seonyoung Park ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Water Extract ◽

Hot Water ◽

Root Extract ◽

Mrna Levels ◽

Ampk Activation ◽

High Fat ◽

Ginger Extract

Ginger is a plant whose rhizome is used as a spice or folk medicine. We aimed to investigate the effect of ginger root extract on obesity and inflammation in rats fed a high-fat diet. Sprague-Dawley rats were divided into three groups and fed either a 45% high-fat diet (HF), HF + hot-water extract of ginger (WEG; 8 g/kg diet), or HF + high-hydrostatic pressure extract of ginger (HPG; 8 g/kg diet) for 10 weeks. The HPG group had lower body weight and white adipose tissue (WAT) mass compared to the HF group. Serum and hepatic lipid levels of HPG group were lower, while fecal lipid excretion of the HPG group was higher than that of the HF group. In the WAT of the WEG and HPG groups, mRNA levels of adipogenic genes were lower than those of the HF group. Moreover, HPG group had lower mRNA levels of pro-inflammatory cytokines than did the HF group. MicroRNA (miR)-21 expression was down-regulated by both WEG and HPG. Additionally, miR-132 expression was down-regulated by HPG. The adenosine monophosphate-activated protein kinase (AMPK) activity of HPG group was greater than that of the HF group. HPG may have beneficial effects on obesity and inflammation, partially mediated by regulation of miR-21/132 expression and AMPK activation in WAT.

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PS-153-The pre-s2 deletion HBVmutants are responsible for the intracellular accumulation of the HBS protein, ER stress and mitochondria dysfunction

Journal of Hepatology ◽

10.1016/s0618-8278(19)30171-9 ◽

2019 ◽

Vol 70 (1) ◽

pp. e97

Author(s):

Jenny Yuh-Jin Liang ◽

Rui-Dung Teng ◽

Cheng-Pu Sun ◽

Chien-Wei Su ◽

Ming-Hua Tao ◽

...

Keyword(s):

Er Stress ◽

Intracellular Accumulation ◽

Mitochondria Dysfunction

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AMP-Activated Protein Kinase Activation during Cardioplegia-Induced Hypoxia/Reoxygenation Injury Attenuates Cardiomyocytic Apoptosis via Reduction of Endoplasmic Reticulum Stress

Mediators of Inflammation ◽

10.1155/2010/130636 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 26

Author(s):

Chi-Hsiao Yeh ◽

Tzu-Ping Chen ◽

Yao-Chang Wang ◽

Yu-Min Lin ◽

Shu-Wen Fang

Keyword(s):

Er Stress ◽

Tunel Staining ◽

Ampk Activation ◽

Kinase Activation ◽

Antiapoptotic Proteins ◽

Unfolded Protein ◽

Protein Kinase Activation ◽

The Unfolded Protein Response ◽

Protein Response ◽

Amp Activated Protein Kinase

Cardioplegic-induced H/R injury results in cardiomyocytic apoptosis. AMPK has been shown to reduce ER stress and the unfolded protein response (UPR). Whether AMPK activation can attenuate cardiomyocytic apoptosis after cardioplegia-induced H/R injury is unknown. Cardiomyocytes were exposed to simulated ischemia by incubation in a hypoxic chamber with intermittent cold cardioplegia solution infusion at 20-minute intervals and subsequently reoxygenated in a normoxic environment. Various doses of AMPK activators (AICAR or metformin) were given 2 days before H/R injury. The cardiomyocytes were harvested after reoxygenation for subsequent examination. With both AMPK activators, the antiapoptotic genes of ER stress and UPR, the subsequent production of proapoptotic proteins was attenuated, and the antiapoptotic proteins were elevated. The activity of the apoptotic effectors of ER stress was also reduced with AMPK activation. Moreover, TUNEL staining showed that AMPK activation significantly reduced the percentage of apoptotic cardiomyocytes after cardioplegia-induced H/R injury. Our results revealed that AMPK activation during cardioplegia-induced H/R injury attenuates cardiomyocytic apoptosis, via enhancement of antiapoptotic and reduction of proapoptotic responses, resulting from lessening ER stress and the UPR. AMPK activation may serve as a future pharmacological target to reduce H/R injury in the clinical setting.

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