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https://www.readbyqxmd.com/read/28422956/chronic-activation-of-ppar%C3%AE-with-fenofibrate-reduces-autophagic-proteins-in-the-liver-of-mice-independent-of-fgf21
#1
Eunjung Jo, Songpei Li, Qingning Liang, Xinmei Zhang, Hao Wang, Terence P Herbert, Trisha A Jenkins, Aimin Xu, Ji-Ming Ye
Autophagy is a catabolic mechanism to degrade cellular components to maintain cellular energy levels during starvation, a condition where PPARα may be activated. Here we report a reduced autophagic capacity in the liver following chronic activation of PPARα with fenofibrate (FB) in mice. Chronic administration of the PPARα agonist FB substantially reduced the levels of multiple autophagy proteins in the liver (Atg3, Agt4B, Atg5, Atg7 and beclin 1) which were associated with a decrease in the light chain LC3II/LC3I ratio and the accumulation of p62...
2017: PloS One
https://www.readbyqxmd.com/read/28415024/glucocorticoids-differentially-regulate-the-innate-immune-responses-of-tlr4-and-the-cytosolic-dna-sensing-pathway
#2
Jinli Wang, Ruining Wang, Jiahui Yang, Xiaofan Yang, Shengfeng Hu, Hui Wang, Chaoying Zhou, Wenjing Xiong, Qian Wen, Li Ma
Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation...
April 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28404910/thalidezine-a-novel-ampk-activator-eliminates-apoptosis-resistant-cancer-cells-through-energy-mediated-autophagic-cell-death
#3
Betty Yuen Kwan Law, Flora Gordillo-Martínez, Yuan Qing Qu, Ni Zhang, Su Wei Xu, Paolo Saul Coghi, Simon Wing Fai Mok, Jianru Guo, Wei Zhang, Elaine Lai Han Leung, Xing Xing Fan, An Guo Wu, Wai Kit Chan, Xiao Jun Yao, Jing Rong Wang, Liang Liu, Vincent Kam Wai Wong
Cancers illustrating resistance towards apoptosis is one of the main factors causing clinical failure of conventional chemotherapy. Innovative therapeutic methods which can overcome the non-apoptotic phenotype are needed. The AMP-activated protein kinase (AMPK) is the central regulator of cellular energy homeostasis, metabolism, and autophagy. Our previous study showed that the identified natural AMPK activator is able to overcome apoptosis-resistant cancer via autophagic cell death. Therefore, AMPK is an ideal pharmaceutical target for chemoresistant cancers...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404589/autophagy-is-activated-to-protect-against-podocyte-injury-in-adriamycin-induced-nephropathy
#4
Mixuan Yi, Lei Zhang, Yu Liu, Man J Livingston, Jian-Kang Chen, N Stanley Nahman, Fuyou Liu, Zheng Dong
Podocytes are highly differentiated epithelial cells wrapping glomerular capillary to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classical model of glomerular disease...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28400112/endothelial-specific-deletion-of-autophagy-related-7-atg7-attenuates-arterial-thrombosis-in-mice
#5
Jonathan W Yau, Krishna K Singh, Yan Hou, Xi Lei, Azza Ramadan, Adrian Quan, Hwee Teoh, Wolfgang M Kuebler, Mohammed Al-Omran, Bobby Yanagawa, Heyu Ni, Subodh Verma
BACKGROUND: Thrombosis persists as a leading cause of morbidity and mortality. Given that endothelial cells (ECs) play a central role in regulating thrombosis, understanding the molecular endothelial cues that regulate susceptibility or resistance to thrombosis have important translational implications. Accordingly, we evaluated the role of endothelial autophagy in the development of thrombosis. METHODS: We generated mice in which the essential autophagy-related 7 (ATG7) gene was conditionally deleted from ECs (EC-ATG7(-/-) mice)...
March 16, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28388958/pre-incubation-with-hucmsc-exosomes-prevents-cisplatin-induced-nephrotoxicity-by-activating-autophagy
#6
Bingying Wang, Haoyuan Jia, Bin Zhang, Juanjuan Wang, Cheng Ji, Xueming Zhu, Yongmin Yan, Lei Yin, Jing Yu, Hui Qian, Wenrong Xu
BACKGROUND: The administration of cisplatin is limited due to its nephrotoxic side effects, and prevention of this nephrotoxicity of cisplatin is difficult. Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel therapeutic approach for tissue injury. In this study, we demonstrated that the pretreatment of human umbilical cord MSC-derived exosomes (hucMSC-Ex) can prevent the development of cisplatin-induced renal toxicity by activation of autophagy in vitro and in vivo...
April 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28386361/downregulation-of-mir-429-contributes-to-the-development-of-drug-resistance-in-epithelial-ovarian-cancer-by-targeting-zeb1
#7
Jing Zou, Ling Liu, Qi Wang, Fuqiang Yin, Zhijun Yang, Wei Zhang, Li Li
Drug resistance is an obstacle to the treatment of epithelial ovarian cancer. Recently, research has suggested that miRNAs (microRNAs) are involved in cancer development, and speculation has been made about their possible involvement in drug resistance. Thus, we attempted to identify selected miRNAs involved in the development of chemo-resistance in epithelial ovarian cancer. Using miRNA profiles of a panel of cisplatin-resistant (SKOV3/DDP) cells, we validated data using quantitative real time-PCR (QRT-PCR), and studied the effects of miR-429 on cancer cell chemo-sensitivity, using gain- and loss-of-function studies...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28376477/osteopontin-promotes-cell-migration-and-invasion-and-inhibits-apoptosis-and-autophagy-in-colorectal-cancer-by-activating-the-p38-mapk-signaling-pathway
#8
Ren-Hong Huang, Ying-Jun Quan, Jin-Hong Chen, Ting-Feng Wang, Ming Xu, Min Ye, Hao Yuan, Chong-Jie Zhang, Xiao-Jian Liu, Zhi-Jun Min
BACKGROUND: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy...
April 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28351322/pvt1-affects-growth-of-glioma-microvascular-endothelial-cells-by-negatively-regulating-mir-186
#9
Yawen Ma, Ping Wang, Yixue Xue, Chengbin Qu, Jian Zheng, Xiaobai Liu, Jun Ma, Yunhui Liu
Vigorous angiogenesis is one of the reasons for the poor prognosis of glioma. A number of studies have shown that long non-coding RNA can affect a variety of biological behaviors of tumors. However, the influence of long non-coding RNAs on glioma vascular endothelial cells remains unclear. To simulate the glioma microenvironment, we applied glioma-conditioned medium to human cerebral microvascular endothelial cells. The long non-coding RNA PVT1 was found to be highly expressed in glioma vascular endothelial cells...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345663/nuclear-localization-of-beclin-1-promotes-radiation-induced-dna-damage-repair-independent-of-autophagy
#10
Fei Xu, Yixuan Fang, Lili Yan, Lan Xu, Suping Zhang, Yan Cao, Li Xu, Xiaoying Zhang, Jialing Xie, Gaoyue Jiang, Chaorong Ge, Ni An, Daohong Zhou, Na Yuan, Jianrong Wang
Beclin 1 is a well-established core mammalian autophagy protein that is embryonically indispensable and has been presumed to suppress oncogenesis via an autophagy-mediated mechanism. Here, we show that Beclin 1 is a prenatal primary cytoplasmic protein but rapidly relocated into the nucleus during postnatal development in mice. Surprisingly, deletion of beclin1 in in vitro human cells did not block an autophagy response, but attenuated the expression of several DNA double-strand break (DSB) repair proteins and formation of repair complexes, and reduced an ability to repair DNA in the cells exposed to ionizing radiation (IR)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342290/verapamil-treatment-induces-cytoprotective-autophagy-by-modulating-cellular-metabolism
#11
Elżbieta Kania, Beata Pająk, Jim O'Prey, Pablo Sierra Gonzalez, Anna Litwiniuk, Kaja Urbańska, Kevin M Ryan, Arkadiusz Orzechowski
Verapamil, an L-type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of verapamil on autophagy and cell viability in greater detail. We report here that verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine (CQ) or by CRISPR/Cas9-mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to verapamil...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28339029/hydroxychloroquine-sensitizes-chronic-myeloid-leukemia-cells-to-v%C3%AE-9v%C3%AE-2-t-cell-mediated-lysis-independent-of-autophagy
#12
Biqing Han, Yanmin Zhao, Yu Lin, Shan Fu, Limengmeng Wang, Mingming Zhang, Ruxiu Tie, Binsheng Wang, Yi Luo, Lizhen Liu, Jian Yu, He Huang
Hydroxychloroquine (HCQ) is the only autophagy inhibitor in clinical use and it has shown great potential in treating chronic myeloid leukemia (CML). By inhibiting autophagy, HCQ enhances the anti-CML efficiency of chemotherapy. In the present study, we demonstrated that HCQ sensitized CML cells to Vγ9Vδ2 T cell-mediated lysis. HCQ inhibited autophagy in CML cells, but the sensitizing effects of HCQ were autophagy-independent. Since the sensitization was not mimicked by ATG7 knockdown and even occurred in the absence of ATG7...
March 24, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28333139/inhibition-of-autophagy-prevents-irradiation-induced-neural-stem-and-progenitor-cell-death-in-the-juvenile-mouse-brain
#13
Yafeng Wang, Kai Zhou, Tao Li, Yiran Xu, Cuicui Xie, Yanyan Sun, Yaodong Zhang, Juan Rodriguez, Klas Blomgren, Changlian Zhu
Radiotherapy is an effective tool in the treatment of malignant brain tumors. However, damage to brain stem and progenitor cells constitutes a major problem and is associated with long-term side effects. Autophagy has been shown to be involved in cell death, and the purpose of this study was to evaluate the effect of autophagy inhibition on neural stem and progenitor cell death in the juvenile brain. Ten-day-old selective Atg7 knockout (KO) mice and wild-type (WT) littermates were subjected to a single 6Gy dose of whole-brain irradiation...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28327001/autophagy-promotes-the-repair-of-radiation-induced-dna-damage-in-bone-marrow-hematopoietic-cells-via-enhanced-stat3-signaling
#14
Fei Xu, Xin Li, Lili Yan, Na Yuan, Yixuan Fang, Yan Cao, Li Xu, Xiaoying Zhang, Lan Xu, Chaorong Ge, Ni An, Gaoyue Jiang, Jialing Xie, Han Zhang, Jiayi Jiang, Xiaotian Li, Lei Yao, Suping Zhang, Daohong Zhou, Jianrong Wang
Autophagy protects hematopoietic cells from radiation damage in part by promoting DNA damage repair. However, the molecular mechanisms by which autophagy regulates DNA damage repair remain largely elusive. Here, we report that this radioprotective effect of autophagy depends on STAT3 signaling in murine bone marrow mononuclear cells (BM-MNCs). Specifically, we found that STAT3 activation and nuclear translocation in BM-MNCs were increased by activation of autophagy with an mTOR inhibitor and decreased by knockout of the autophagy gene Atg7...
March 2017: Radiation Research
https://www.readbyqxmd.com/read/28323983/autophagic-degradation-of-collagen-1a1-by-cortisol-in-human-amnion-fibroblasts
#15
Yabing Mi, Wangsheng Wang, Chuyue Zhang, Chao Liu, Jiangwen Lu, Wenjiao Li, Rujuan Zuo, Leslie Myatt, Kang Sun
Rupture of fetal membranes can initiate parturition at both term and preterm. Collagen is the crucial factor determining the tensile strength of the membranes. Toward the end of gestation, a feed-forward regeneration of cortisol via 11β-hydroxysteroid dehydrogenase 1 exists in fetal membranes. It remains undetermined whether cortisol contributes to collagen reduction in fetal membranes. In this study, we have examined whether cortisol accumulation is a causative factor for collagen reduction in human amnion fibroblasts, the major source of collagens in the membranes...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320092/inhibition-of-pi3k-akt-mtor-signaling-pathway-promotes-autophagy-of-articular-chondrocytes-and-attenuates-inflammatory-response-in-rats-with-osteoarthritis
#16
Jian-Feng Xue, Zhong-Min Shi, Jian Zou, Xiao-Lin Li
OBJECTIVE: This study aims to explore the relationship between PI3K/AKT/mTOR signaling pathway and autophagy of articular chondrocytes in rats with osteoarthritis (OA). METHODS: Rat articular chondrocytes were isolated and cultured, and then induced by protein inhibitors of PI3K/AKT/mTOR signaling pathway. Chondrocytes were assigned into blank group, IL-1β induction group (IL-1β group), PI3K inhibitor+IL-1β induction group (PI3Ki+IL-1β group), AKT inhibitor+IL-1β induction group (AKTi+IL-1β group) and mTOR inhibitor+IL-1β induction group (mTORi+IL-1β group)...
March 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28304100/cartilage-specific-autophagy-deficiency-promotes-er-stress-and-impairs-chondrogenesis-in-perk-atf4-chop-dependent-manner
#17
Xiaomin Kang, Wei Yang, Dongxu Feng, Xinxin Jin, Zhengmin Ma, Zhuang Qian, Tianping Xie, Huixia Li, Jiali Liu, Ruiqi Wang, Fang Li, Danhui Li, Hongzhi Sun, Shufang Wu
Autophagy is activated during nutritionally depleted or hypoxic conditions to facilitate cell survival. Because growth plate is an avascular and hypoxic tissue, autophagy may have a crucial role during chondrogenesis; however, the functional role and underlying mechanism of autophagy in regulation of growth plate remains elusive. In this study, we generated (TamCart) Atg7(-/-) (Atg7cKO) mice to explore the role of autophagy during endochondral ossification. Atg7cKO mice exhibited growth retardation associated with reduced chondrocyte proliferation and differentiation, and increased chondrocyte apoptosis...
March 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28299793/foxo1-ampk-ulk1-regulates-ethanol-induced-autophagy-in-muscle-by-enhanced-atg14-association-with-the-becn1-pik3c3-complex
#18
Ly Q Hong-Brown, C Randell Brown, Maithili Navaratnarajah, Charles H Lang
BACKGROUND: Excessive alcohol (EtOH) consumption causes an imbalance in protein metabolism. EtOH impairs protein synthesis in C2C12 myoblasts via a FoxO1-AMPK-TSC2-mTORC1 pathway and also induces protein degradation. As the underlying regulatory signaling cascades for these processes are currently poorly defined, we tested the hypothesis that alcohol-induced autophagy is mediated via activation of the PIK3C3 complex that is regulated by FoxO1-AMPK. METHODS: C2C12 myoblasts were incubated with EtOH for various periods of time, and autophagy pathway-related proteins were assessed by Western blotting and immunoprecipitation...
March 16, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28286171/epigallocatechin-3-gallate-increases-autophagy-signaling-in-resting-and-unloaded-plantaris-muscles-but-selectively-suppresses-autophagy-protein-abundance-in-reloaded-muscles-of-aged-rats
#19
Hideyuki Takahashi, Yutaka Suzuki, Junaith S Mohamed, Takafumi Gotoh, Suzette L Pereira, Stephen E Alway
We have previously found that Epigallocatechin-3-gallate (EGCg), an abundant catechin in green tea, reduced apoptotic signaling and improved muscle recovery in response to reloading after hindlimb suspension (HS). In this study, we investigated if EGCg altered autophagy signaling in skeletal muscle of old rats in response to HS or reloading after HS. Fischer 344×Brown Norway inbred rats (age 34months) were given 1ml/day of purified EGCg (50mg/kg body weight), or the same sample volume of the vehicle by gavage...
June 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28285998/a-non-cell-autonomous-role-of-bec-1-becn1-beclin1-in-coordinating-cell-cycle-progression-and-stem-cell-proliferation-during-germline-development
#20
Kristina Ames, Dayse S Da Cunha, Brenda Gonzalez, Marina Konta, Feng Lin, Gabriel Shechter, Lev Starikov, Sara Wong, Hannes E Bülow, Alicia Meléndez
The decision of stem cells to proliferate and differentiate is finely controlled. The Caenorhabditis elegans germline provides a tractable system for studying the mechanisms that control stem cell proliferation and homeostasis [1-4]. Autophagy is a conserved cellular recycling process crucial for cellular homeostasis in many different contexts [5], but its function in germline stem cell proliferation remains poorly understood. Here, we describe a function for autophagy in germline stem cell proliferation. We found that autophagy genes such as bec-1/BECN1/Beclin1, atg-16...
March 20, 2017: Current Biology: CB
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