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https://www.readbyqxmd.com/read/28813167/lipophagy-maintains-energy-homeostasis-in-the-kidney-proximal-tubule-during-prolonged-starvation
#1
Satoshi Minami, Takeshi Yamamoto, Yoshitsugu Takabatake, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Tomonori Kimura, Jun-Ya Kaimori, Isao Matsui, Takayuki Hamano, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Yoshitaka Isaka
Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use. The involvement of autophagy in lipid metabolism in the kidney remains largely unknown. Here, we investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation using PTC-specific Atg5-deficient (atg5-TSKO) mice and an in vitro serum starvation model...
August 16, 2017: Autophagy
https://www.readbyqxmd.com/read/28798804/sinomenine-hydrochloride-attenuates-renal-fibrosis-by-inhibiting-excessive-autophagy-induced-by-adriamycin-an-experimental-study
#2
Ming-Ming Zhao, Bin Yang, Qiu Zhang, Jin-Hu Wang, Jin-Ning Zhao, Yu Zhang
The objective of this study is to investigate if sinomenine hydrochloride (SIN-HCl) could be effective against adriamycin-induced renal fibrosis by regulating autophagy in a rat model. Forty male Sprague-Dawley (SD) rats were randomly divided into control group, model group, telmisartan group, and SIN-HCl group; rat model was induced by adriamycin; all rats were given intragastric administration for 6 weeks. Urine was collected from rats in metabolic cages to determine 24 h protein level. This was done after intragastric administration for the first two weeks and then once for every two weeks...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28796254/sunitinib-induces-genomic-instability-of-renal-carcinoma-cells-through-affecting-the-interaction-of-lc3-ii-and-parp-1
#3
Siyuan Yan, Ling Liu, Fengxia Ren, Quan Gao, Shanshan Xu, Bolin Hou, Yange Wang, Xuejun Jiang, Yongsheng Che
Deficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB)...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791309/research-progress-on-mechanism-of-podocyte-depletion-in-diabetic-nephropathy
#4
REVIEW
Haoran Dai, Qingquan Liu, Baoli Liu
Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28772211/autophagy-as-a-potential-therapeutic-target-during-epithelial-to-mesenchymal-transition-in-renal-cell-carcinoma-an-in-vitro-study
#5
Mamta Singla, Shalmoli Bhattacharyya
Cancer progression toward invasive and metastatic disease is aided by reactivation of epithelial-mesenchymal transition (EMT), involving transdifferentiation of epithelial cells into mesenchymal phenotype. This leads to increased migratory and stem cell-like features in the cells. These EMT cells are more resistant to chemotherapy and it is hypothesized that the phenomenon of autophagy induces resistance, providing a survival strategy for cells. In the present study, we induced EMT-like phenotype in renal carcinoma cells and identified corresponding higher autophagy flux in these cells...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28757338/soluble-epoxide-hydrolase-in-podocytes-is-a-significant-contributor-to-renal-function-under-hyperglycemia
#6
Ahmed Bettaieb, Shinichiro Koike, Ming-Fo Hsu, Yoshihiro Ito, Samah Chahed, Santana Bachaalany, Artiom Gruzdev, Miguel Calvo-Rubio, Kin Sing Stephen Lee, Bora Inceoglu, John D Imig, Jose M Villalba, Darryl C Zeldin, Bruce D Hammock, Fawaz G Haj
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of renal failure, and podocyte dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH, encoded by Ephx2) is a conserved cytosolic enzyme whose inhibition has beneficial effects on renal function. The aim of this study is to investigate the contribution of sEH in podocytes to hyperglycemia-induced renal injury. MATERIALS AND METHODS: Mice with podocyte-specific sEH disruption (pod-sEHKO) were generated, and alterations in kidney function were determined under normoglycemia, and high-fat diet (HFD)- and streptozotocin (STZ)-induced hyperglycemia...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28740545/e-selectin-targeted-sialic-acid-peg-dexamethasone-micelles-for-enhanced-anti-inflammatory-efficacy-for-acute-kidney-injury
#7
Jing-Bo Hu, Xu-Qi Kang, Jing Liang, Xiao-Juan Wang, Xiao-Ling Xu, Ping Yang, Xiao-Ying Ying, Sai-Ping Jiang, Yong-Zhong Du
The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis(x) antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65...
2017: Theranostics
https://www.readbyqxmd.com/read/28733250/sphingosine-kinase-1-protects-renal-tubular-epithelial-cells-from-renal-fibrosis-via-induction-of-autophagy
#8
Chunyang Du, Yunzhuo Ren, Fang Yao, Jialiang Duan, Hui'er Zhao, Yunxia Du, Xia Xiao, Huijun Duan, Yonghong Shi
Autophagy is an important homoeostatic mechanism for the lysosomal degradation of protein aggregates and damaged cytoplasmic components. Recent studies suggest that autophagy which is induced by TGF-β1 suppresses kidney fibrosis in renal tubular epithelial cells (RTECs) of obstructed kidneys. Sphingosine kinase 1(SK1), converting sphingosine into endogenous sphingosine-1-phosphate (S1P), was shown to modulate autophagy and involved in the processes of fibrotic diseases. Since SK1 activity is also up-regulated by TGF-β1, we explored its effect on the induction of autophagy and development of renal fibrosis in this study...
July 18, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28729036/molecular-mechanisms-of-renal-aging
#9
REVIEW
Roland Schmitt, Anette Melk
Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28717191/mln4924-pevonedistat-a-protein-neddylation-inhibitor-suppresses-proliferation-and-migration-of-human-clear-cell-renal-cell-carcinoma
#10
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
#11
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
#12
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
#13
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
#14
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease-activated receptor-2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, is central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In the present 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...
August 2, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28692436/andrographolide-enhances-cisplatin-mediated-anticancer-effects-in-lung-cancer-cells-through-blockade-of-autophagy
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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