TRAM1 protect HepG2 cells from palmitate induced insulin resistance through ER stress-JNK pathway

Tang, Zhuqi; Zhang, Wanlu; Wan, Chunhua; Xu, Guofeng; Nie, Xiaobing; Zhu, Xiaohui; Xia, Nana; Zhao, Yun; Wang, Suxin; Cui, Shiwei; Wang, Cuifang

doi:10.1016/j.bbrc.2015.01.027

Cited by 22 publications

(13 citation statements)

References 16 publications

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“…Consistent with these views, we found that palmitate induced insulin resistance in HUVECs in time- and concentration-dependent manners ( Figures 1A,B ). Moreover, palmitate-induced insulin resistance was accompanied with enhanced ER stress ( Figure 2A ), which has been suggested a major contributor to palmitate-induced insulin resistance through ER stress-activated JNK/IRS-1 pathway (Chan et al, 2013; Simon-Szabó et al, 2014; Tang et al, 2015; Park et al, 2016). Indeed, our results found that palmitate stimulated JNK/IRS-1 pathway ( Figures 4C,D ).…”

Section: Discussionmentioning

confidence: 98%

RETRACTED: Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

Qian

Zhang

et al. 2017

Front. Pharmacol.

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Dysfunction of proteasome and autophagy will result in disturbance of endoplasmic reticulum (ER) proteostasis, and thus lead to long-term and chronic ER stress and subsequent unfolded protein response (UPR), which is implicated in the occurrence and development of insulin resistance. Curcumin exerts beneficial metabolic effects in in vitro cells and in vivo animal models of diabetes and diabetic complications including cardiovascular diseases, due to its powerful anti-oxidative and anti-inflammatory properties. However, its impacts on insulin resistance of endothelial cells and its underlying mechanism(s) remain ill-defined. Herein, we tested the hypothesis that curcumin action in ER protein quality control was related to improvement of insulin resistance in human umbilical vein endothelial cells (HUVECs) cultured with saturated fatty acid palmitate. We found that palmitate treatment induced insulin resistance of HUVECs and activated both the ubiquitin-proteasome system (UPS) and autophagy. Palmitate-stimulated activation of the UPS and autophagy was attenuated by pharmacological inhibition of ER stress. In addition, curcumin supplementation mitigated palmitate-induced insulin resistance, inhibited the UPS, and activated autophagy. Furthermore, curcumin administration suppressed palmitate-induced protein aggregation and ER stress. Genetic inhibition of autophagy by silencing autophagy protein 5 (Atg5) completely restored total protein ubiquitination and protein aggregation in HUVECs treated with combined curcumin and palmitate. Atg5-knockdown also abolished the beneficial effects of curcumin on palmitate-induced ER stress, JNK/IRS-1 pathway as well as insulin signaling. Our results reveal that curcumin-activated autophagy could maintain proteostasis in ER leading to attenuation of ER stress and subsequent inhibition of JNK/IRS-1 pathway and improvement of insulin resistance.

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Section: Discussionmentioning

confidence: 98%

RETRACTED: Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

Qian

Zhang

et al. 2017

Front. Pharmacol.

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“…18,24) Although NF-kB and JNK are chronically activated in heart failure and diabetes mellitus, there is still disagreement as to whether they have a protective or detrimental role. [25][26][27] However, TNFR1/2 are important bridges for extracellular and intracellular inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients

Zhang

et al. 2017

Int. Heart J.

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SummaryInflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86).TNFR1/2 were significantly higher in patients with heart failure and diabetes mellitus based on mRNA expression to protein expression and serum expression. However, there were no differences in mRNA, protein, and serum levels of TNFR1/2 between the HF group and DM group. Furthermore, there were no differences between the groups in some traditional serum inflammatory markers.This study demonstrated higher expressions of TNFR, NF-kB, and JNK in patients with heart failure and diabetes mellitus. Compared with traditional serum markers, TNFR1 and TNFR2 are associated with heart failure risk in type 2 diabetes mellitus patients. (Int Heart J 2017; 58: 245-249)

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“…Studies have shown that JNK is involved in ER stress-induced apoptosis in lung epithelial cells 43 and HeLa cells 44 . Additionally, the concomitant occurrence of both ER stress markers and JNK activation indicate that JNK activation occurs downstream of ER stress 45 and that the ER stress-JNK pathway plays an important role in mediating insulin resistance and apoptosis 46 47 .…”

Section: Discussionmentioning

confidence: 99%

Ganoderma lucidum polysaccharide peptide prevents renal ischemia reperfusion injury via counteracting oxidative stress

Zhong

Wang

Liu

et al. 2015

Sci Rep

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Ganoderma lucidum polysaccharide peptide (GLPP) scavenges oxygen free radicals that are a key factor in the pathogenesis of renal ischemia reperfusion injury (RIRI). The aim of this study was to determine whether GLPP could attenuate RIRI by counteracting the oxidative stress. The mechanism involved was assessed by an in vivo mouse RIRI model and an in vitro hypoxia/reoxygenation model, and tunicamycin-stimulated NRK-52E cells were used to explore the GLPP-mediated alleviation of ER stress. Experimental results showed that renal dysfunction and morphological damage were reduced in GLPP-treated group. The imbalance of redox status was reversed and production of ROS was reduced by GLPP. RIRI-induced mitochondrial- and ER stress-dependent apoptosis were dramatically inhibited in GLPP-treated group. Intriguingly, JNK activation in the kidney with RIRI or hypoxia/reoxygenation was inhibited by GLPP. These results suggest that the protective effect of GLPP against RIRI may be due to reducing oxidative stress, alleviating the mitochondrial and ER stress-dependent apoptosis caused by excessive ROS.

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TRAM1 protect HepG2 cells from palmitate induced insulin resistance through ER stress-JNK pathway

Cited by 22 publications

References 16 publications

RETRACTED: Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

RETRACTED: Curcumin Improves Palmitate-Induced Insulin Resistance in Human Umbilical Vein Endothelial Cells by Maintaining Proteostasis in Endoplasmic Reticulum

TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients

Ganoderma lucidum polysaccharide peptide prevents renal ischemia reperfusion injury via counteracting oxidative stress

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