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https://www.readbyqxmd.com/read/28992279/targeting-new-cellular-disease-pathways-in-autosomal-dominant-polycystic-kidney-disease
#1
Ming-Yang Chang, Albert C M Ong
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of end-stage renal failure. Understanding the molecular and cellular pathogenesis of ADPKD could help to identify new targets for treatment. The classic cellular cystic phenotype includes changes in proliferation, apoptosis, fluid secretion, extracellular matrix and cilia function. Hoever, recent research, suggests that the cellular cystic phenotype could be broader and that changes, such as altered metabolism, autophagy, inflammation, oxidative stress and epigenetic modification, could play important roles in the processes of cyst initiation, cyst growth or disease progression...
August 29, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28987240/protein-tyrosine-phosphatase-1b-deficiency-in-podocytes-mitigates-hyperglycemia-induced-renal-injury
#2
Yoshihiro Ito, Ming-Fo Hsu, Ahmed Bettaieb, Shinichiro Koike, Aline Mello, Miguel Calvo-Rubio, Jose M Villalba, Fawaz G Haj
OBJECTIVE: Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. METHODS: To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO)...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28981387/aldh1a1-and-hltf-modulate-the-activity-of-lysosomal-autophagy-inhibitors-in-cancer-cells
#3
Shengfu Piao, Rani Ojha, Vito W Rebecca, Arabinda Samanta, Xiao-Hong Ma, Quentin Mcafee, Michael C Nicastri, Meghan Buckley, Eric Brown, Jeffrey D Winkler, Phyllis A Gimotty, Ravi K Amaravadi
Lysosomal autophagy inhibitors (LAI) such as hydroxychloroquine (HCQ) have significant activity in a subset of cancer cell lines. LAIs are being evaluated in cancer clinical trials, but genetic determinants of sensitivity to LAIs are unknown, making it difficult to predict which tumors would be most susceptible. Here we characterize differentially expressed genes in HCQ-sensitive (-S) and -resistant (-R) cancer cells. Notably, expression of canonical macroautophagy/autophagy genes was not associated with sensitivity to HCQ...
October 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28974016/high-endogenous-accumulation-of-%C3%AF-3-polyunsaturated-fatty-acids-protect-against-ischemia-reperfusion-renal-injury-through-ampk-mediated-autophagy-in-fat-1-mice
#4
Do Hyeong Gwon, Tae Woong Hwang, Ju-Ye Ro, Yoon-Joong Kang, Jin Young Jeong, Do-Kyung Kim, Kyu Lim, Dong Woon Kim, Dae Eun Choi, Jwa-Jin Kim
Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms...
September 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28970584/endoplasmic-reticulum-stress-the-unfolded-protein-response-and-autophagy-in-kidney-diseases
#5
REVIEW
Andrey V Cybulsky
Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1α) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis...
October 3, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28948792/in-vitro-anticancer-activity-and-in-vivo-biodistribution-of-rhenium-i-tricarbonyl-aqua-complexes
#6
Kevin M Knopf, Brendan L Murphy, Samantha N MacMillan, Jeremy M Baskin, Martin P Barr, Eszter Boros, Justin J Wilson
Seven rhenium(I) complexes of the general formula fac-[Re(CO)3(NN)(OH2)](+) where NN = 2,2'-bipyridine (8), 4,4'-dimethyl-2,2'-bipyridine (9), 4,4'-dimethoxy-2,2'-bipyridine (10), dimethyl 2,2'-bipyridine-4,4'-dicarboxylate (11), 1,10-phenanthroline (12), 2,9-dimethyl-1,10-phenanthroline (13), or 4,7-diphenyl-1,10-phenanthroline (14), were synthesized and characterized by (1)H NMR spectroscopy, IR spectroscopy, mass spectrometry, and X-ray crystallography. With the exception of 11, all complexes exhibited 50% growth inhibitory concentration (IC50) values that were less than 20 μM in HeLa cells, indicating that these compounds represent a new potential class of anticancer agents...
October 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28947349/contribution-of-inflammatory-pathways-to-fabry-disease-pathogenesis
#7
REVIEW
Paula Rozenfeld, Sandro Feriozzi
Lysosomal storage diseases are usually considered to be pathologies in which the passive deposition of unwanted materials leads to functional changes in lysosomes. Lysosomal deposition of unmetabolized glycolipid substrates stimulates the activation of pathogenic cascades, including immunological processes, and particularly the activation of inflammation. In lysosomal storage diseases, the inflammatory response is continuously being activated because the stimulus cannot be eliminated. Consequently, inflammation becomes a chronic process...
September 13, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28944925/autophagy-is-activated-to-protect-renal-tubular-epithelial-cells-against-iodinated-contrast-media%C3%A2-induced-cytotoxicity
#8
Na Liu, Rong Lei, Mi-Mi Tang, Wei Cheng, Min Luo, Qian Xu, Shao-Bin Duan
With the steady increase in the use of various contrast‑related technologies in recent years, contrast‑induced nephropathy has received significant attention from clinicians and researchers. The present study aimed to determine the potential role of autophagy in iodinated contrast media (CM)‑induced cell injury and apoptosis in human proximal renal tubular epithelial HK‑2 cells. The present study used the iodinated CM iohexol (200 mg iodine/ml) to treat HK‑2 cells for 6 h, in order to establish a damaged cell model...
September 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944924/cyclic-helix-b-peptide-protects-hk%C3%A2-2-cells-from-oxidative-stress-by-inhibiting-er-stress-and-activating-nrf2-signalling-and-autophagy
#9
Long Li, Miao Lin, Lexi Zhang, Shang Huang, Chao Hu, Long Zheng, Liping Li, Chao Zhang, Cheng Yang, Yaqiu Long, Ruiming Rong, Tongyu Zhu
Renal ischemia‑reperfusion injury (IRI) is present in numerous diseases and is observed following certain treatments, including renal transplantation. Preventing tubular epithelial cells (TECs) from undergoing apoptosis is vital for treatment of renal IRI. Cyclic helix B peptide (CHBP) is a novel agent that has a protective effect on renal IRI in vivo. In the present study, the effect and underlying mechanism of CHBP on TECs was investigated. The HK‑2 human renal proximal tubular epithelial cell line was treated with 500 µmol/l H2O2 for 4 h prior to determining the effect of CHBP pretreatment for 1 h on cell viability, caspase 3 activity and expression levels, expression levels of oxidative stress markers, endoplasmic reticulum (ER) stress markers, NF‑E2‑related factor 2 (Nrf2), heme oxygenase‑1 (HO‑1) and autophagy markers...
September 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28943243/hucmsc-exosome-transported-14-3-3%C3%AE-prevents-the-injury-of-cisplatin-to-hk-2-cells-by-inducing-autophagy-in-vitro
#10
REVIEW
Juanjuan Wang, Haoyuan Jia, Bin Zhang, Lei Yin, Fei Mao, Jing Yu, Cheng Ji, Xiao Xu, Yongmin Yan, Wenrong Xu, Hui Qian
BACKGROUND AIMS: On the basis of previous studies, exosomes secreted by human umbilical cord mesenchymal stromal cell (hucMSC-ex) could prevent and repair acute kidney injury induced by cisplatin in rats. However, its potential mechanism is still unclear. In the present study, the model with hucMSC-ex pretreated human renal tubular epithelial cell lines HK-2 that could prevent the injury of cisplatin was successfully established. METHODS: First, we pretreated the HK-2 cells with hucMSC-ex for 24 h...
September 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28929674/-molecular-mechanisms-of-autophagy-in-regulating-renal-aging-and-interventional-effects-of-chinese-herbal-medicine
#11
REVIEW
Yue Tu, Wei Sun, Di-Ping Chen, Yi-Gang Wan, Wei Wu, Jian Yao
Aging is the gradual functional recession of the living tissues or organs caused by a variety of genetic and environmental factors together. Autophagy is a process of degrading cytoplasmic components mediated by lysosomes in eukaryotic cells. Kidney is a typical target organ of aging. Autophagy regulates renal aging. Decrease in autophagy can accelerate renal aging,whereas,increase in autophagy can delay renal aging. During the process of regulating renal aging,the mammalian target of rapamycin (mTOR) and its related signaling pathways including the adenosine monophosphate activated protein kinase (AMPK)/mTOR,the phosphatidylinositol 3-kinase (PI3K)/ serine-threonine kinase(Akt)/mTOR,the AMPK/silent information regulation 1 (Sirt1) and transforming growth factor β (TGF-β) play the important roles in renal aging...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28923830/the-role-of-crp-and-atg9b-expression-in-clear-cell-renal-cell-carcinoma
#12
Zheng Ma, Zengguang Qi, Jiangsong Li, Jing Yang, Zhonghua Xu
Background: The purpose of the study is to investigate the correlation between the expression of C-reactive protein ( CRP ) and autophagy-related 9B ( ATG9B ) and pathological features of clear cell renal cell carcinoma (CCRCC) patients. We also intended to explore the effects of manipulated expression of CRP and ATG9B on the apoptosis and cell cycle progressing of CCRCC cell line. Material and Methods : ATG9B expression in CCRCC tissues and adjacent renal tissues was analyzed by immunohistochemistry (IHC)...
September 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28918350/expression-and-functional-characterization-of-the-bnip3-protein-in-renal-cell-carcinomas
#13
Stephan Macher-Goeppinger, Martina Keith, Gencay Hatiboglu, Markus Hohenfellner, Peter Schirmacher, Wilfried Roth, Katrin E Tagscherer
BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) is a BH3-only protein that regulates apoptosis and autophagy. BNIP3 plays also an important role in hypoxia-induced cell response and is regulated by HIF1. Here, we studied a possible association of BNIP3 expression and the prognosis of patients with renal cell carcinomas (RCCs) and examined the functional relevance of BNIP3 in the regulation of cell survival and apoptosis of renal carcinoma cells. BNIP3 expression was determined by immunohistochemistry in RCC tumor tissue samples of 569 patients using a tissue microarray...
September 14, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28889337/the-cellular-selection-between-apoptosis-and-autophagy-roles-of-vitamin-d-glucose-and-immune-response-in-diabetic-nephropathy
#14
Magda Hamzawy, Sarah Ali Abdelhameed Gouda, Laila Rashid, Mary Attia Morcos, Heba Shoukry, Nivin Sharawy
BACKGROUND AND AIMS: Apoptosis, autophagy and cell cycle arrest are cellular responses to injury which are supposed to play fundamental roles in initiation and progression of diabetic nephropathy (DN). The aims of the present study is to shed light on the potential effects of vitamin D analog 22-oxacalcitriol (OCT) on different cell responses during DN, and the possible interplay between both glucose, immune system and vitamin D in determining the cell fate. METHOD: All rats were randomly allocated into one of three groups: control, vehicle-treated DN group and OCT-treated DN group...
September 9, 2017: Endocrine
https://www.readbyqxmd.com/read/28888852/renal-endoplasmic-reticulum-stress-is-coupled-to-impaired-autophagy-in-a-mouse-model-of-gsd-ia
#15
Benjamin L Farah, Dustin J Landau, Yajun Wu, Rohit A Sinha, Alwin Loh, Boon-Huat Bay, Dwight D Koeberl, Paul M Yen
GSD Ia (von Gierke Disease, Glycogen Storage Disease Type Ia) is a devastating genetic disorder with long-term sequelae, such as non-alcoholic fatty liver disease and renal failure. Down-regulated autophagy is involved in the development of hepatic metabolic dysfunction in GSD Ia; however, the role of autophagy in the renal pathology is unknown. Here we show that autophagy is impaired and endoplasmic reticulum (ER) stress is increased in the kidneys of a mouse model of GSD Ia. Induction of autophagy by rapamycin also reduces this ER stress...
September 1, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28886014/downregulation-of-autophagy-is-associated-with-severe-ischemia-reperfusion-induced-acute-kidney-injury-in-overexpressing-c-reactive-protein-mice
#16
Ao Bian, Mingjun Shi, Brianna Flores, Nancy Gillings, Peng Li, Shirley Xiao Yan, Beth Levine, Changying Xing, Ming Chang Hu
C-reactive protein (CRP), was recently reported to be closely associated with poor renal function in patients with acute kidney injury (AKI), but whether CRP is pathogenic or a mere biomarker in AKI remains largely unclear. Impaired autophagy is known to exacerbate renal ischemia-reperfusion injury (IRI). We examined whether the pathogenic role of CRP in AKI is associated with reduction of autophagy. We mated transgenic rabbit CRP over-expressing mice (Tg-CRP) with two autophagy reporter mouse lines, Tg-GFP-LC3 mice (LC3) and Tg-RFP-GFP-LC3 mice (RG-LC3) respectively to generate Tg-CRP-GFP-LC3 mice (PLC3) and Tg-CRP-RFP-GFP-LC3 mice (PRG-LC3)...
2017: PloS One
https://www.readbyqxmd.com/read/28871310/autophagy-in-diabetic-kidney-disease-regulation-pathological-role-and-therapeutic-potential
#17
REVIEW
Danyi Yang, Man J Livingston, Zhiwen Liu, Guie Dong, Ming Zhang, Jian-Kang Chen, Zheng Dong
Diabetic kidney disease, a leading cause of end-stage renal disease, has become a serious public health problem worldwide and lacks effective therapies. Autophagy is a highly conserved lysosomal degradation pathway that removes protein aggregates and damaged organelles to maintain cellular homeostasis. As important stress-responsive machinery, autophagy is involved in the pathogenesis of various diseases. Emerging evidence has suggested that dysregulated autophagy may contribute to both glomerular and tubulointerstitial pathologies in kidneys under diabetic conditions...
September 4, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28871079/sirt6-deficiency-exacerbates-podocyte-injury-and-proteinuria-through-targeting-notch-signaling
#18
Min Liu, Kaili Liang, Junhui Zhen, Meng Zhou, Xiaojie Wang, Ziying Wang, Xinbing Wei, Yan Zhang, Yu Sun, Zhuanli Zhou, Hua Su, Chun Zhang, Ningjun Li, Chengjiang Gao, Jun Peng, Fan Yi
Podocyte injury is a major determinant of proteinuric kidney disease and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance. Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling. Sirt6 is downregulated in renal biopsies from patients with podocytopathies and its expression correlates with glomerular filtration rate. Podocyte-specific deletion of Sirt6 exacerbates podocyte injury and proteinuria in two independent mouse models, diabetic nephropathy, and adriamycin-induced nephropathy...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28860615/aggravation-of-acute-kidney-injury-by-mpges-2-down-regulation-is-associated-with-autophagy-inhibition-and-enhanced-apoptosis
#19
Ting Li, Ying Liu, Jie Zhao, Shuying Miao, Yunfei Xu, Ke Liu, Meidong Liu, Guiliang Wang, Xianzhong Xiao
The deletion of microsomal prostaglandin E synthase-2 (mPGES-2) does not affect in vivo PGE2 production, and the function of this enzyme remains unknown until now. This study investigated the expression and roles of mPGES-2 in LPS induced acute kidney injury (AKI) both in vitro and in vivo. We found that mPGES-2 was up-regulated in kidney of mice with LPS induced AKI. Inhibition of mouse mpges2 gene expression exacerbated LPS-induced renal dysfunction, renal tubular cell damage and apoptosis, while inhibited kidney autophagy...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837139/apelin-involved-in-progression-of-diabetic-nephropathy-by-inhibiting-autophagy-in-podocytes
#20
Yu Liu, Jia Zhang, Yangjia Wang, Xiangjun Zeng
Podocyte autophagy dysfunction has been reported to be responsible for the progression of diabetic nephropathy (DN), however, the factors contributed to autophagy dysfunction in type 2 diabetes are not fully understood. Among promoting factors in DN, an adipokine, apelin, had been showed to trigger podocyte dysfunction. Therefore, it is hypothesized that apelin, which is increased in plasma in type 2 diabetes, lead to podocyte apoptosis through inhibiting podocyte autophagy, which resulted in podocyte dysfunction followed by DN...
August 24, 2017: Cell Death & Disease
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