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https://www.readbyqxmd.com/read/28445528/baicalein-protects-rat-insulinoma-ins-1-cells-from-palmitate-induced-lipotoxicity-by-inducing-ho-1
#1
Hyun Jeong Kwak, Dongki Yang, Yongha Hwang, Hee-Sook Jun, Hyae Gyeong Cheon
OBJECTIVE: β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1...
2017: PloS One
https://www.readbyqxmd.com/read/28439080/ets-related-gene-mediated-androgen-receptor-aggregation-and-endoplasmic-reticulum-stress-in-prostate-cancer-development
#2
Taduru L Sreenath, Shiela S Macalindong, Natallia Mikhalkevich, Shashwat Sharad, Ahmed Mohamed, Denise Young, Talaibek Borbiev, Charles Xavier, Rishita Gupta, Muhammad Jamal, Kevin Babcock, Shyh-Han Tan, Marja T Nevalainen, Albert Dobi, Gyorgy Petrovics, Isabell A Sesterhenn, Inger L Rosner, Charles J Bieberich, Peter Nelson, Valeri Vasioukhin, Shiv Srivastava
Mechanistic studies of deregulated ERG in prostate cancer and other cancers continue to enhance its role in cancer biology and its utility as a biomarker and therapeutic target. Here, we show that ERG, through its physical interaction with androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436023/activation-of-amp-activated-protein-kinase-by-metformin-ablates-angiotensin-ii-induced-endoplasmic-reticulum-stress-and-hypertension-in-mice-in-vivo
#3
Quanlu Duan, Ping Song, Ye Ding, Ming-Hui Zou
BACKGROUND AND PURPOSE: Metformin, one of the most frequently prescribed medications for type 2 diabetes, reportedly exerts blood pressure (BP)-lowering effects in patients with diabetes; however, the effects and underlying mechanisms of metformin on BP in non-diabetic condition remains to be determined. The aim of the present study was to determine the effects of metformin on angiotensin II (Ang II) infusion-induced hypertension in vivo. EXPERIMENTAL APPROACH: The effects of metformin on BP were investigated in wild-type (WT, C57BL/6 J) and AMP-activated protein kinase (AMPKα2) knockout (AMPKα2(-/-) ) mice with or without Ang II-infusion...
April 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28433751/elevated-chaperone-proteins-are-a-feature-of-winter-freeze-avoidance-by-larvae-of-the-goldenrod-gall-moth-epiblema-scudderiana
#4
Guijun Zhang, Janet M Storey, Kenneth B Storey
Winter survival for many insect species includes a need to maintain metabolic homeostasis and structural/functional integrity of macromolecules not only over a wide range of cold temperatures but also in response to rapid temperature change. Chaperones are well-known to protect/stabilize protein structure with regard to heat stress but less is known about their potential involvement in long-term protection of the proteome at subzero temperatures. The present study assessed the participation of chaperone proteins in the cold hardiness of larvae of the goldenrod gall moth, Epiblema scudderiana (Clemens) (Lepidoptera, Olethreutidae), monitoring changes in nine proteins over the winter months as well as their responses to laboratory cold acclimation or anoxia exposure...
April 19, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/28433684/activating-transcription-factor-6-dependent-sestrin-2-induction-ameliorates-er-stress-mediated-liver-injury
#5
Kyung Hwan Jegal, Sang Mi Park, Sam Seok Cho, Sung Hui Byun, Sae Kwang Ku, Sang Chan Kim, Sung Hwan Ki, Il Je Cho
Endoplasmic reticulum (ER) stress is characterized by an accumulation of misfolded proteins, and ER stress reduction is essential for maintaining tissue homeostasis. However, the molecular mechanisms that protect cells from ER stress are not completely understood. The present study investigated the role of sestrin 2 (SESN2) on ER stress and sought to elucidate the mechanism responsible for the hepatoprotective effect of SESN2 in vitro and in vivo. Treatment with tunicamycin (Tm) increased SESN2 protein and mRNA levels and reporter gene activity...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28426781/tauroursodeoxycholic-acid-tudca-attenuates-pressure-overload-induced-cardiac-remodeling-by-reducing-endoplasmic-reticulum-stress
#6
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Jin Ock Kim, Mi Young Lee, Wan Seok Kang, Yong Sook Kim, Youngkeun Ahn, Woo Jin Park, Chunghee Cho, Do Han Kim
Pressure overload in the heart induces pathological hypertrophy and is associated with cardiac dysfunction. Apoptosis and fibrosis signaling initiated by the endoplasmic reticulum stress (ERS) is known to contribute to these maladaptive effects. The aim of this study was to investigate whether reduction of ERS by a known chemical chaperone, tauroursodeoxycholic acid (TUDCA) can attenuate pressure overload-induced cardiac remodeling in a mouse model of transverse aortic constriction (TAC). Oral administration of TUDCA at a dose of 300 mg/kg body weight (BW) in the TUDCA-TAC group reduced ERS markers (GRP78, p-PERK, and p-eIf2α), compared to the Vehicle (Veh)-TAC group...
2017: PloS One
https://www.readbyqxmd.com/read/28424579/grp78-at-the-centre-of-the-stage-in-cancer-and-neuroprotection
#7
REVIEW
Caty Casas
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28423613/secreted-grp78-activates-egfr-src-stat3-signaling-and-confers-the-resistance-to-sorafeinib-in-hcc-cells
#8
Rui Li, Gu Yanjiao, He Wubin, Wang Yue, Huang Jianhua, Zheng Huachuan, Su Rongjian, Luan Zhidong
Acquired resistance is a common phenomenon for HCC patients who undergone sorafenib treatment, however the mechanism by which acquired resistance develops remains elusive. In this study, we found that GRP78 could be detected in the serum samples of HCC patients and the conditional medium of multiple HCC cell lines, suggesting that GRP78 is secreted by HCC cells. Further studies showed that secreted GRP78 facilitated the proliferation and inhibited the apoptosis induced by sorafenib both in HCC cell lines and in tumor xenografts...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420170/fisetin-protects-pc12-cells-from-tunicamycin-mediated-cell-death-via-reactive-oxygen-species-scavenging-and-modulation-of-nrf2-driven-gene-expression-sirt1-and-mapk-signaling-in-pc12-cells
#9
Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen, Ming-Jiuan Wu
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416388/human-grp78-affinity-towards-its-signaling-partners-ire1%C3%AE-and-perk-is-differently-modulated-by-an-unfolded-protein-client
#10
Razvan C Stan, Raissa L Silva, Maristela M de Camargo
Protein-folding stress is characteristic of specialized secretory cells and plays a dominant role in a multitude of diseases. The unfolded protein response (UPR) thus triggered is a proteostatic signaling network that adapts the protein-folding capacity of the endoplasmic reticulum to the cellular demands. We have measured the binding affinities between human GRP78, an essential chaperone located in ER, and two transmembrane UPR sensors (human PERK and Ire1α), with or without the addition of an unfolded protein client...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28415750/xanthohumol-induces-paraptosis-of-leukemia-cells-through-p38-mitogen-activated-protein-kinase-signaling-pathway
#11
Xiangquan Mi, Chunming Wang, Chao Sun, Xu Chen, Xiang Huo, Yiming Zhang, Gang Li, Bo Xu, Jun Zhang, Jianxin Xie, Zhenhua Wang, Ji Li
Xanthohumol as a natural polyphenol demonstrates an anticancer activity, but its underlying mechanism remains unclear. In this study, we showed that xanthohumol (XN) induces paraptosis of leukemia cells. The paraptosis is one cell death which is characterized by dilation of the endoplasmic reticulum and/or mitochondria. The results demonstrated that XN treatment significantly inhibited cell proliferation and triggered extensive cytoplasmic vacuolation of HL-60 leukemia cells, but it did not cause the cleavage of caspase-3 protein or apoptosis...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415630/resveratrol-alleviates-ffa-and-ccl4-induced-apoptosis-in-hepg2-cells-via-restoring-endoplasmic-reticulum-stress
#12
Fenghua Li, Yang Yang, Lili Yang, Kai Wang, Xing Zhang, Yunlong Zong, Yixin Ding, Changhong Wang, Li Zhang, Guang Ji
Cell apoptosis often induces inflammation and injury in the liver, with endoplasmic reticulum (ER) stress as the most possible reason. Resveratrol (RSV) has been shown to prevent hepatic steatosis and alleviate apoptosis, however, the exact mechanisms underlying the effects still need to be explored. Here we co-cultured HepG2 cells with free fatty acid (FFA) solution (oleic acid: palmitic acid = 2:1) and then exposed to a carbon tetrachloride (CCl4) solution to induce apoptosis. To evaluate the therapeutic effects, RSV (2...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28411010/effects-of-vitamin-d-and-resveratrol-on-metabolic-associated-markers-in-liver-and-adipose-tissue-from-samp8-mice
#13
Yehua Rui, Jinbo Cheng, Liqiang Qin, Cheng Shan, Jie Chang, Guiping Wang, Zhongxiao Wan
SAMP8 mice exhibit multiple metabolic characteristics associated with age, and it is a suitable candidate for researching aging associated metabolic dysfunction. OBJECTIVES: We aimed to 1) explore how key metabolic markers will be altered in both liver and adipose tissue with aging in SAMP8 mice; and 2) how the combination of vitamin D (VD) with resveratrol (RSV) will affect aging associated metabolic impairment in liver and adipose tissue from SAMP8 mice. METHODS: SAMP8 mice and their control SAMR1 mice were divided into 5 groups, i...
April 11, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28407787/glucose-regulated-protein-78-demonstrates-antiviral-effects-but-is-more-suitable-for-hepatocellular-carcinoma-prevention-in-hepatitis-b
#14
Nai Q Zheng, Zi H Zheng, Hai X Xu, Ming X Huang, Xiao M Peng
BACKGROUND: Hepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78 (GRP78) can inhibit HBV replication, but promote virion secretion and hepatocellular cancer cell invasion. For these reasons, the overall effect of GRP78 on HBV production and whether to utilize the HBV replication-inhibitory effect of GRP78 up-regulation or the hepatocellular cancer cell invasion-inhibitory effect of its down-regulation were further investigated in order to improve the efficacy of current antiviral therapy...
April 13, 2017: Virology Journal
https://www.readbyqxmd.com/read/28405686/long-non-coding-rna-meg3-induces-cell-apoptosis-in-esophageal-cancer-through-endoplasmic-reticulum-stress
#15
Zhen-Lun Huang, Rui-Pei Chen, Xiao-Tao Zhou, Hao-Lian Zhan, Min-Min Hu, Bin Liu, Guan-Di Wu, Ling-Fei Wu
Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as cell growth, apoptosis and migration. Although downregulation of lncRNA MEG3 has been identified in several cancers, little is known about its role in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to detect MEG3 expression in clinical ESCC tissues, investigate its biological functions and the endoplasmic reticulum (ER) stress-relative mechanism. MEG3 expression levels were detected by qRT-PCR in both tumor tissues and adjacent non-tumor tissues from 28 ESCC patients...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28402954/chaperone-mediated-autophagy-compensates-for-impaired-macroautophagy-in-the-cirrhotic-liver-to-promote-hepatocellular-carcinoma
#16
Srinivas Chava, Christine Lee, Yucel Aydin, Partha K Chandra, Asha Dash, Milad Chedid, Swan N Thung, Krzysztof Moroz, Tong Wu, Nabeen C Nayak, Srikanta Dash
Macroautophagy and chaperone-mediated autophagy (CMA) represent two major lysosomal degradation processes and often compensate for one another to facilitate cell survival. The aim of this study was to determine whether these autophagy pathways could compensate for one another to promote HCC cell survival in the cirrhotic liver. Analysis of normal liver tissue showed no expression of glypican-3 or p62 proteins, suggesting that macroautophagy is the major contributor to autophagic flux under non-pathological conditions...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400209/astaxanthin-attenuates-glutamate-induced-apoptosis-via-inhibition-of-calcium-influx-and-endoplasmic-reticulum-stress
#17
Xiaotong Lin, Yan Zhao, Shanhe Li
Astaxanthin (AST) is a carotenoid that has been shown to have neuroprotective effects. In this study, it was found that AST significantly inhibited glutamate-induced loss of cell viability and apoptosis. AST pretreatment attenuated glutamate-induced activation of caspase-3, reduction of anti-apoptotic protein Bcl-2, and increase of pro-apoptotic protein Bak. In addition, AST pretreatment suppressed the production of intracellular reactive oxygen species. AST treatment also prevented glutamate-induced increase of the level of activated p38 mitogen-activated protein kinase (MAPK), which has been shown to promote apoptotic events...
April 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28399139/ibutilide-treatment-protects-against-er-stress-induced-apoptosis-by-regulating-calumenin-expression-in-tunicamycin-treated-cardiomyocytes
#18
Yu Wang, Liying Xuan, Xiaoxue Cui, Yilin Wang, Shaoqing Chen, Chengxi Wei, Ming Zhao
BACKGROUND: Ibutilide, a class III antiarrhythmic agent has been shown to be cardioprotective in treating atrial fibrillation, promoting cardioconversion and recently this agent has been shown to protect against ER stress induced apoptosis in cardiomyocytes. In this study we begin to identify the mechanism by which ibutilide exerts its cardioprotection in tunicamycin treated cardiomyocytes. We examined ER stress markers including calumenin; a calcium binding ER chaperone protein that has recently been linked to ER stress in cardiomyocytes, in our treated cells...
2017: PloS One
https://www.readbyqxmd.com/read/28397086/structure-activity-relationship-of-piperine-and-its-synthetic-amide-analogs-for-therapeutic-potential-to-prevent-experimentally-induced-er-stress-in-vitro
#19
Ayat S Hammad, Sreenithya Ravindran, Ashraf Khalil, Shankar Munusamy
Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells...
April 10, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28394345/cripto-and-its-signaling-partner-grp78-drive-the-metastatic-phenotype-in-human-osteotropic-prostate-cancer
#20
E Zoni, L Chen, S Karkampouna, Z Granchi, E I Verhoef, F La Manna, J Kelber, R C M Pelger, M D Henry, E Snaar-Jagalska, G J L H van Leenders, L Beimers, P Kloen, P C Gray, G van der Pluijm, M Kruithof-de Julio
CRIPTO (CR-1, TDGF1) is a cell surface/secreted oncoprotein actively involved in development and cancer. Here, we report that high expression of CRIPTO correlates with poor survival in stratified risk groups of prostate cancer (PCa) patients. CRIPTO and its signaling partner glucose-regulated protein 78 (GRP78) are highly expressed in PCa metastases and display higher levels in the metastatic ALDH(high) sub-population of PC-3M-Pro4Luc2 PCa cells compared with non-metastatic ALDH(low). Coculture of the osteotropic PC-3M-Pro4Luc2 PCa cells with differentiated primary human osteoblasts induced CRIPTO and GRP78 expression in cancer cells and increases the size of the ALDH(high) sub-population...
April 10, 2017: Oncogene
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