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https://www.readbyqxmd.com/read/28717191/mln4924-pevonedistat-a-protein-neddylation-inhibitor-suppresses-proliferation-and-migration-of-human-clear-cell-renal-cell-carcinoma
#1
Shuai Tong, Yang Si, Hefen Yu, Lingqiang Zhang, Ping Xie, Wenguo Jiang
Neddylation is a post-translational protein modification associated with cancer development. MLN4924 is a neddylation inhibitor currently under investigation in multiple phase I studies on various malignancies, and its clincal name is Pevonedistat. It has been documented that MLN4924 blocks Cullins neddylation and inactivates CRLs and, in turn, triggers cell-cycle arrest, apoptosis, senescence and autophagy in many cancer cells. In this study, we investigated the anti-tumor effect of MLN4924 in human clear cell renal carcinoma (ccRCC)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714586/activation-of-autophagy-is-involved-in-the-protective-effect-of-17%C3%AE-oestradiol-on-endotoxaemia-induced-multiple-organ-dysfunction-in-ovariectomized-rats
#2
Ming-Tzeung Chung, Yen-Mei Lee, Hsin-Hsueh Shen, Pao-Yun Cheng, Yu-Chen Huang, Yu-Ju Lin, Yu-Yang Huang, Kwok-Keung Lam
Oestrogens have been reported to attenuate acute inflammation in sepsis. In this study, the effects of long-term oestrogen replacement with 17β-oestradiol (E2 ) on endotoxaemia-induced circulatory dysfunction and multiple organ dysfunction syndrome were evaluated in ovariectomized (Ovx) rats. E2 (50 μg/kg, s.c., 3 times/week) was administered for 8 weeks, followed by the induction of endotoxaemia by intravenous infusion of lipopolysaccharides (LPS; 30 mg/kg/4 hrs). Oestrogen deficiency induced by ovariectomy for 9 weeks augmented the LPS-induced damage, including endotoxic shock, myocardial contractile dysfunction, renal dysfunction and rhabdomyolysis...
July 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28706237/suppressed-autophagic-response-underlies-augmentation-of-renal-ischemia-reperfusion-injury-by-type-2-diabetes
#3
Shingo Muratsubaki, Atsushi Kuno, Masaya Tanno, Takayuki Miki, Toshiyuki Yano, Hirohito Sugawara, Satoru Shibata, Koki Abe, Satoko Ishikawa, Kouhei Ohno, Yukishige Kimura, Yuki Tatekoshi, Kei Nakata, Wataru Ohwada, Masashi Mizuno, Tetsuji Miura
Diabetes mellitus is a major risk factor for acute kidney injury (AKI). Here, we hypothesized that suppression of autophagic response underlies aggravation of renal ischemia/reperfusion (I/R) injury by type 2 diabetes mellitus (T2DM). In OLETF, a rat model of T2DM, and its non-diabetic control, LETO, AKI was induced by unilateral nephrectomy and 30-min occlusion and 24-h reperfusion of the renal artery in the contralateral kidney. Levels of serum creatinine and blood urea nitrogen and tubular injury score after I/R were significantly higher in OLETF than in LETO...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705935/forkhead-box-o3-foxo3-regulates-kidney-tubular-autophagy-following-urinary-tract-obstruction
#4
Ling Li, Ronald Zviti, Catherine Ha, Zhao V Wang, Joseph A Hill, Fangming Lin
Autophagy has been shown to be important for normal homeostasis and adaptation to stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial autophagy are not fully understood. Here, we explored the role of the stress-responsive transcription factor forkhead box O3 (FoxO3) in mediating injury-induced proximal tubular autophagy in mice with unilateral ureteral obstruction (UUO). We show that following UUO, FoxO3 is activated and displays nuclear expression in the hypoxic proximal tubules exhibiting high levels of autophagy...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28694352/protease-activated-receptor-2-promotes-kidney-tubular-epithelial-inflammation-by-inhibiting-autophagy-via-the-pi3k-akt-mtor-signalling-pathway
#5
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease activated receptors 2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, are central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In this study, we examine the effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related inflammation and reveal the underlying mechanism involved. Autophagic activity and levels of autophagic marker LC3 were examined in human kidney tubular epithelial cells with PAR2 knockdown or overexpression...
July 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#6
Daolu Yuwen, Shanwei Mi, Yuzhu Ma, Wenjie Guo, Qiang Xu, Yan Shen, Yongqian Shu
Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells...
July 7, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28669728/targeting-neddylation-pathway-with-mln4924-pevonedistat-induces-noxa-dependent-apoptosis-in-renal-cell-carcinoma
#7
Jiyou Wang, Shiwen Wang, Wenjuan Zhang, Xiaofang Wang, Xiaojun Liu, Liang Liu, Lihui Li, Yupei Liang, Jinha Yu, Lak Shin Jeong, Lijun Jia, Hu Zhao, Yanmei Zhang
Inhibition of protein neddylation pathway has emerged an attractive anticancer strategy in preclinical studies by using Nedd8-activating enzyme (NAE) inhibitor MLN4924 (Pevonedistat). Previous studies have reported the antitumor activity of MLN4924 mediated by its efficacy on apoptosis, autophagy and senescence. However, whether MLN4924 has any effect on renal carcinoma cells (RCC) remains unexplored. Here we reported that MLN4924 specifically inhibited protein neddylation pathway, leading to statistically significantly suppress the proliferation, survival and migration of RCC cells by inducing G2 cell-cycle arrest, followed by apoptosis in a MLN4924 dose-dependent manner...
June 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28656209/hydrogen-sulfide-reduced-renal-tissue-fibrosis-by-regulating-autophagy-in-diabetic-rats
#8
Lin Li, Ting Xiao, Fang Li, Yan Li, Ou Zeng, Maojun Liu, Biao Liang, Zining Li, Chun Chu, Jun Yang
The present study aimed to explore the effect of hydrogen sulfide (H2S) on renal tissue fibrosis and its mechanism in diabetic rats. Rats were randomly divided into four groups (n=13/group): Control group; induced diabetes mellitus group (STZ); induced diabetes mellitus treated with H2S group (STZ + H2S); normal rats treated with H2S group (H2S). The diabetic model was induced by intraperitoneal (i.p.) injections of 40 mg/kg body weight streptozotocin (STZ); the control group was treated with saline every day (i...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28635397/induction-of-apoptosis-and-autophagy-by-calcifying-nanoparticles-in-human-bladder-cancer-cells
#9
Ji-Hua Wu, Yao-Liang Deng, Quan Liu, Jun-Chuan Yu, Yun-Long Liu, Zi-Qi He, Xiao-Feng Guan
Calcifying nanoparticles have been linked to various types of human disease, but how they contribute to disease processes is unclear. Here, we examined whether and how calcifying nanoparticles isolated from patients with kidney stones are cytotoxic to human bladder cancer cells. Calcifying nanoparticles were isolated from midstream urine of patients with renal calcium oxalate stones and examined by electron microscopy. Human bladder cancer cells (EJ cells) were cultured in the presence of calcifying nanoparticles or nanohydroxyapatites for 12 and 72 h and examined for toxicity using the Cell Counting Kit-8, for autophagy using transmission electron microscopy and confocal microscopy, and for apoptosis using fluorescence microscopy, transmission electron microscopy, and flow cytometry...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28627693/renal-denervation-attenuates-cardiac-hypertrophy-in-spontaneously-hypertensive-rats-via-regulation-of-autophagy
#10
Jionghua Huang, He Huang, Wei Pan, Dejin Ou, Wenjun Dai, Yuhui Lin, Jinlei Wu, Wenjie Xie, Ximing Chen
It has been suggested that renal denervation (RD) may attenuate left ventricular (LV) hypertrophy. However, the role that autophagy serves in this process is currently unclear. In the present study, utilizing a model of hypertension‑induced cardiac hypertrophy in spontaneous hypertensive rats, it was demonstrated that RD was significantly associated with a reduction in LV hypertrophy. Furthermore, a decrease in the myocardial mRNA of hypertrophy‑associated genes was demonstrated in RD rats compared with sham controls...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627643/niclosamide-attenuates-inflammatory-cytokines-via-the-autophagy-pathway-leading-to-improved-outcomes-in-renal-ischemia-reperfusion-injury
#11
Lin-Xia Zhang, Hui-Juan Zhao, Dong-Li Sun, Shan-Lin Gao, Hong-Mei Zhang, Xin-Guo Ding
Renal ischemia/reperfusion (I/R) injury is a debilitating condition that leads to loss renal function and damage to kidney tissue in the majority of patients with acute kidney disease. Previous studies have indicated that autophagy serves a protective function in renal I/R injury. In the present study, the effect of the anthelmintic niclosamide in the regulation of inflammatory responses in kidney I/R was investigated. A total of 40 Sprague-Dawley rats were randomly divided into the following 5 groups (n=8 in each group): Sham group; renal I/R injury; renal I/R injury plus 3‑methyladenine (3‑MA) treatment (15 mg/kg); renal I/R injury plus niclosamide (25 mg/kg); and renal I/R injury plus rapamycin (10 mg/kg)...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624441/hsp90-inhibitor-geldanamycin-attenuates-the-cytotoxicity-of-sunitinib-in-cardiomyocytes-via-inhibition-of-the-autophagy-pathway
#12
Takayuki Kimura, Mai Uesugi, Kazuma Takase, Norimasa Miyamoto, Kohei Sawada
Sunitinib malate (sunitinib) is an orally available, multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. Although sunitinib is effective for the treatment of patients with gastrointestinal stromal tumor, advanced renal cell carcinoma, or pancreatic neuroendocrine tumor, adverse cardiac events associated with sunitinib administration have been reported. Here, we examined the effect of geldanamycin, an inhibitor of heat shock protein (Hsp) 90, on sunitinib-induced cytotoxicity in cardiomyocytes...
June 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28619945/transcriptional-activation-of-ragd-gtpase-controls-mtorc1-and-promotes-cancer-growth
#13
Chiara Di Malta, Diletta Siciliano, Alessia Calcagni, Jlenia Monfregola, Simona Punzi, Nunzia Pastore, Andrea N Eastes, Oliver Davis, Rossella De Cegli, Angela Zampelli, Luca G Di Giovannantonio, Edoardo Nusco, Nick Platt, Alessandro Guida, Margret Helga Ogmundsdottir, Luisa Lanfrancone, Rushika M Perera, Roberto Zoncu, Pier Giuseppe Pelicci, Carmine Settembre, Andrea Ballabio
The mechanistic target of rapamycin complex 1 (mTORC1) is recruited to the lysosome by Rag guanosine triphosphatases (GTPases) and regulates anabolic pathways in response to nutrients. We found that MiT/TFE transcription factors-master regulators of lysosomal and melanosomal biogenesis and autophagy-control mTORC1 lysosomal recruitment and activity by directly regulating the expression of RagD. In mice, this mechanism mediated adaptation to food availability after starvation and physical exercise and played an important role in cancer growth...
June 16, 2017: Science
https://www.readbyqxmd.com/read/28599504/combination-of-wogonin-and-sorafenib-effectively-kills-human-hepatocellular-carcinoma-cells-through-apoptosis-potentiation-and-autophagy-inhibition
#14
Li-Wen Rong, Rui-Xue Wang, Xue-Lian Zheng, Xu-Qin Feng, Lei Zhang, Lin Zhang, Yong Lin, Zhi-Ping Li, Xia Wang
The small molecule multi-kinase inhibitor sorafenib has become the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC) and renal cell carcinoma. Similar to other kinase inhibitors, drug resistance hinders its clinical use; thus, combination therapy to improve sorafenib sensitivity is a promising approach. The present study shows for the first time that the combination of sorafenib and wogonin exerts a significant potentiation of cytotoxicity in a number of human HCC cell lines in a dose-dependent manner...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28597089/vosalophen-a-vanadium-complex-with-a-stilbene-derivative-induction-of-apoptosis-autophagy-and-efficiency-in-experimental-cutaneous-leishmaniasis
#15
Patrícia de A Machado, Jessica O F Morais, Gustavo S G Carvalho, Wallace P Lima, Gilson C Macedo, Elizandra A Britta, Celso V Nakamura, Adilson D da Silva, Alexandre Cuin, Elaine S Coimbra
In our previous work, we demonstrated the promising in vitro effect of VOSalophen, a vanadium complex with a stilbene derivative, against Leishmania amazonensis. Its antileishmanial activity has been associated with oxidative stress in L. amazonensis promastigotes and L. amazonensis-infected macrophages. In the present study, the mechanism involved in the death of parasites after treatment with VOSalophen, as well as in vivo effect in the murine model cutaneous leishmaniasis, has been investigated. Promastigotes of L...
August 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28594408/autophagy-blockade-and-lysosomal-membrane-permeabilization-contribute-to-lead-induced-nephrotoxicity-in-primary-rat-proximal-tubular-cells
#16
Xiang-Bin Song, Gang Liu, Fei Liu, Zhen-Gui Yan, Zhen-Yong Wang, Zong-Ping Liu, Lin Wang
Lead (Pb) is a known nephrotoxicant that causes damage to proximal tubular cells. Autophagy has an important protective role in various renal injuries, but the role of autophagy in Pb-elicited nephrotoxicity remains largely unknown. In this study, Pb promoted the accumulation of autophagosomes in primary rat proximal tubular (rPT) cells, and subsequent findings revealed that this autophagosome accumulation was caused by the inhibition of autophagic flux. Moreover, Pb exposure did not affect the autophagosome-lysosome fusion in rPT cells...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28593583/regulating-autophagy-as-a-therapeutic-target-for-diabetic-nephropathy
#17
REVIEW
Munehiro Kitada, Yoshio Ogura, Itaru Monno, Daisuke Koya
PURPOSE OF REVIEW: Autophagy promotes cellular health in response to various cellular stresses and to changes in nutrient conditions. In this review, we focus on the role of autophagy in the pathogenesis of diabetic nephropathy and discuss the regulation of autophagy as a new therapeutic target for the suppression of diabetic nephropathy. RECENT FINDINGS: Previous studies have indicated that autophagy deficiency or insufficiency in renal cells, including podocytes, mesangial cells, endothelial cells and tubular cells, contributes to the pathogenesis of diabetic nephropathy...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28577326/trivalent-chromium-induces-autophagy-by-activating-sphingomyelin-phosphodiesterase-2-and-increasing-cellular-ceramide-levels-in-renal-hk2-cells
#18
Cheng-Lin Yang, Shiow-Her Chiou, Wei-Chun Tai, Nithila A Joseph, Kuan-Chih Chow
In this study, we examined the role of autophagy in the initiation of lipid increases in renal epithelial HK2 cells. We found that trivalent chromium [Cr(III)] induced autophagy by activating sphingomyelin phosphodiesterase 2 (SMPD2). SMPD2 increases levels of ceramide and other lipids. Confocal immunofluorescence microscopy showed that signals of ceramide overlapped with LC3, suggesting that ceramide might play an important role in the formation of autophagosome. In conclusion, our data indicate that Cr(III) induces autophagy via structural aberration of organelle membrane, in particular by the increase of lipid compositions in addition to autophagy-associated proteins...
June 3, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28560694/role-of-apoptosis-in-the-development-of-autosomal-dominant-polycystic-kidney-disease-adpkd
#19
REVIEW
Lukas Peintner, Christoph Borner
Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disorder in the Western world and is characterized by cystogenesis that often leads to end-stage renal disease (ESRD). Mutations in the pkd1 gene, encoding for polycystin-1 (PC1) and its interaction partner pkd2, encoding for polycystin-2 (PC2), are the main drivers of this disease. PC1 and PC2 form a multiprotein membrane complex at cilia sites of the plasma membrane and at intracellular membranes. This complex mediates calcium influx and stimulates various signaling pathways regulating cell survival, proliferation and differentiation...
July 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28544853/microrna-34a-protect-myocardial-cells-against-ischemia-reperfusion-injury-through-inhibiting-autophagy-via-regulating-tnf%C3%AE-expression
#20
Haifeng Shao, Lili Yang, Li Wang, Bozan Tang, Jian Wang, Qiang Li
BACKGROUND: Ischemia/reperfusion (I/R) accompanying with the blood supply restored after myocardial infarction. Myocardial I/R injury relieves when autophagy decreased. MicroRNA-34a(miR-34a) regulate autophagy in renal I/R injury model. But whether it can affect cardiac I/R injury remains studying. This study investigated how miR-34a in protecting myocardial cells against I/R injury through inhibit autophagy via regulating tumor necrosis factor α (TNFα) . METHODS: Constructed the I/R model in vivo with Langendorff; treated Neonatal Rat cardiomyocyte to make H/R injury model in vitro with hypoxia/reoxygenation (H/R) method...
May 25, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
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