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https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#1
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29446736/gene-therapy-in-kidney-transplantation-evidence-of-efficacy-and-future-directions
#2
Jiawei Li, Guisheng Qi, Guowei Tu, Cheng Yang, Ruiming Rong
Allograft loss remains a severe clinical problem after kidney transplantation. The molecular mechanism of graft loss is a complex process involving T and/or B cell activation, inflammation responses, autophagy and apoptosis. Since these pathways are involved in immune responses in kidney transplant rejection, application of genetic interference to inhibit specific pathways could present an effective targeted gene therapy method. Recent studies have successfully attempted to use gene therapy to target the key molecules involved in immune responses during transplantation...
February 13, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29446059/the-novel-involvement-of-podocyte-autophagic-activity-in-the-pathogenesis-of-lupus-nephritis
#3
Juan Jin, Meiyu Ye, Li Zhao, Wenli Zou, Wei Shen, Hongjuan Zhang, Jianguang Gong, Qiang He
BACKGROUND: Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated...
February 15, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29446053/systems-pharmacological-analysis-of-mitochondrial-cardiotoxicity-induced-by-selected-tyrosine-kinase-inhibitors
#4
Tanaya Vaidya, Jeff Kamta, Maher Chaar, Anusha Ande, Sihem Ait-Oudhia
Tyrosine kinase inhibitors (TKIs) are targeted therapies rapidly becoming favored over conventional cytotoxic chemotherapeutics. Our study investigates two FDA approved TKIs, DASATINIB; indicated for IMATINIB-refractory chronic myeloid leukemia, and SORAFENIB; indicated for hepatocellular carcinoma and advanced renal cell carcinoma. Limited but crucial evidence suggests that these agents can have cardiotoxic side effects ranging from hypertension to heart failure. A greater understanding of the underlying mechanisms of this cardiotoxicity are needed as concerns grow and the capacity to anticipate them is lacking...
February 14, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29444517/acetyl-coa-synthetase-2-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-upregulating-lysosomal-associated-membrane-protein-1-expression
#5
Lv Yao, Xiaoqiang Guo, Yaoting Gui
BACKGROUND/AIMS: Reprogramming energy metabolism is an emerging hallmark of many cancers, and this alteration is especially evident in renal cell carcinomas (RCCs). However, few studies have been conducted on lipid metabolism. This study investigated the function and mechanism of lipid metabolism-related acetyl-CoA synthetase 2 (ACSS2) in RCC development, cell migration and invasion. METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression of ACSS2 in cancer tissue and adjacent tissue...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#6
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29435125/inhibition-of-autophagy-attenuated-calcium-oxalate-crystal-induced-renal-tubular-epithelial-cell-injury-in-vivo-and-in-vitro
#7
Yunlong Liu, Derong Li, Ziqi He, Quan Liu, Jihua Wu, Xiaofeng Guan, Zhiwei Tao, Yaoliang Deng
Accumulating evidence suggests that autophagy is involved in the pathophysiological processes of kidney diseases. However, the role of autophagy in the formation of calcium oxalate (CaOx) nephrolithiasis remains unclear. In this study, we investigated the effects of autophagy on renal tubular epithelial cell injury induced by CaOx crystals in vivo and in vitro . We first observed that the expression levels of LC3-II and BECN1 and number of autophagic vacuoles were markedly increased in the renal tissue of CaOx stone patients...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435010/chloroquine-potentiates-the-anticancer-effect-of-sunitinib-on-renal-cell-carcinoma-by-inhibiting-autophagy-and-inducing-apoptosis
#8
Man-Li Li, You-Zhi Xu, Wen-Jie Lu, Yong-Huai Li, Shi-Sheng Tan, Hong-Jun Lin, Tian-Ming Wu, Yan Li, Si-Ying Wang, Ying-Lan Zhao
Sunitinib based adjuvant chemotherapy combined with chloroquine (CQ) for the treatment of renal cell carcinoma (RCC) is in clinical trials; however, its anti-RCC effect and the mechanism remain unclear. In the present study, the anti-RCC effect of sunitinib with CQ and the underlying mechanism was investigated. An MTT assay demonstrated that CQ enhanced the proliferation inhibitory effect of sunitinib against the OS-RC-2 RCC cell line. CQ inhibited sunitinib-induced autophagy in OS-RC-2, which was evidenced by the inhibition of autophagic vacuoles, acidic vesicular organelle formation, light chain 3 (LC3)-II recruitment to the autophagosomes and the conversion of LC3-I to LC3-II, as induced by sunitinib...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29425932/ablation-of-c-ebp-homologous-protein-attenuates-renal-fibrosis-after-ureteral-obstruction-by-reducing-autophagy-and-microtubule-disruption
#9
Mi Ra Noh, Chang-Hoon Woo, Mae-Ja Park, Jee In Kim, Kwon Moo Park
Fibrosis is an undesirable consequence of injury and a critical problem in many diseases. Recent studies have demonstrated an association of C/EBP homologous protein (CHOP) with fibrosis. We investigated the mechanism of CHOP in kidney fibrosis progression after unilateral ureteral obstruction (UUO) using Chop gene-deleted (Chop-/-) mice and their wild-type littermates (Chop+/+). UUO-induced kidney fibrosis was reduced in the Chop-/- than Chop+/+ mice. After UUO, CHOP expression was detected in the cytosol and nucleus of distal tubule cells and collecting duct cells of the kidney...
February 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29425694/renal-fibrosis-primacy-of-the-proximal-tubule
#10
REVIEW
Leslie S Gewin
Tubulointerstitial fibrosis (TIF) is the hallmark of chronic kidney disease and best predictor of renal survival. Many different cell types contribute to TIF progression including tubular epithelial cells, myofibroblasts, endothelia, and inflammatory cells. Previously, most of the attention has centered on myofibroblasts given their central importance in extracellular matrix production. However, emerging data focuses on how the response of the proximal tubule, a specialized epithelial segment vulnerable to injury, plays a central role in TIF progression...
February 6, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29425466/mesenchymal-stem-cells-pretreated-with-melatonin-ameliorate-kidney-functions-in-a-rat-model-of-diabetic-nephropathy
#11
Laila A Rashed, Samah Elattar, Nashwa Eltablawy, Hend Ashour, Lamiaa Mohamed, Yasmin El-Esawy
The aim of this study was to investigate the effect of Melatonin (MT) pretreated mesenchymal stem cells (MSCs) regenerative therapy, as a new therapeutic target in modifying underlying diabetic nephropathy (DN) pathogenesis in a rat model, and its possible effect on autophagy protein Beclin-1. Forty adult male Wistar albino rats divided into four groups: control, DN, MSCs treated (MSCs) and In-vitro Melatonin (5µM for 24 hours) pre-incubated MSCs treated group (MSCs+MT). MSCs treatment significantly improved the renal functions with amelioration of the measured underlying DN pathogenesis and elevation of Beclin-1 protein levels compared to DN group...
February 9, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29424891/autophagy-suppresses-the-proliferation-of-renal-carcinoma-cell
#12
Z-L Wang, Q Deng, T Chong, Z-M Wang
OBJECTIVE: To investigate the effetcs of autophagy on the proliferation of renal carcinoma (RCCs). MATERIALS AND METHODS: Authophagy related protein 7 (Atg7)-overexpressing and knockdown RCC cell lines were established using lentiviral transfection and shRNA interference, respectively. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) (MTT) was used to determine the Cell growth rate, and western blot was used to determine the expression of protein...
January 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29388190/association-study-of-genetic-variation-in-the-autophagy-lysosome-pathway-genes-and-risk-of-eight-kinds-of-cancer
#13
Juan Tan, Linna Fu, Haoyan Chen, Jian Guan, Yingxuan Chen, Jingyuan Fang
The autophagy lysosome pathway is essential to maintain cell viability and homeostasis in response to many stressful environments, which is reported to play a vital role in cancer development and therapy. However, the association of genetic alterations of this pathway with risk of cancer remains unclear. Based on genome-wide association study data of eight kinds of cancer, we used an adaptive rank truncated product approach to perform a pathway-level and gene-level analysis, and used a logistic model to calculate SNP-level associations to examine whether an altered autophagy lysosome pathway contributes to cancer susceptibility...
February 1, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29371637/cell-death-based-approaches-in-treatment-of-the-urinary-tract-associated-diseases-a-fight-for-survival-in-the-killing-fields
#14
REVIEW
Diego Martin-Sanchez, Miguel Fontecha-Barriuso, Maria Dolores Sanchez-Niño, Adrian M Ramos, Ramiro Cabello, Carmen Gonzalez-Enguita, Andreas Linkermann, Ana Belén Sanz, Alberto Ortiz
Urinary tract-associated diseases comprise a complex set of disorders with a variety of etiologic agents and therapeutic approaches and a huge global burden of disease, estimated at around 1 million deaths per year. These diseases include cancer (mainly prostate, renal, and bladder), urinary tract infections, and urolithiasis. Cell death plays a key role in the pathogenesis and therapy of these conditions. During urinary tract infections, invading bacteria may either promote or prevent host cell death by interfering with cell death pathways...
January 25, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29371333/mechanisms-in-endocrinology-sglt2-inhibitors-clinical-benefits-by-restoration-of-normal-diurnal-metabolism
#15
Russell L Esterline, Allan Vaag, Jan Oscarsson, Jiten Vora
Type 2 diabetes (T2D) is associated with inhibition of autophagic and lysosomal housekeeping processes that detrimentally affect key organ functioning; a process likely to be exacerbated by conventional insulin-driven anabolic therapies. We propose that the cardio-renal benefits demonstrated with sodium-glucose cotransporter-2 inhibitor (SGLT2i) treatment in T2D partly may be explained by their ability to drive consistent, overnight periods of increased catabolism brought about by constant glucosuria. Key steps driving this catabolic mechanism include: a raised glucagon/insulin ratio initially depleting glycogen in the liver and ultimately activating gluconeogenesis utilizing circulating amino acids (AAs); a general fuel switch from glucose to free fatty acids (accompanied by a change in mitochondrial morphology from a fission to a sustained fusion state driven by a decrease in AA levels); a decrease in circulating AAs and insulin driving inhibition of mammalian target of rapamycin complex 1 (mTORC1), which enhances autophagy/lysosomal degradation of dysfunctional organelles, eventually causing a change in mitochondrial morphology from a fission to a sustained fusion state...
January 25, 2018: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29367621/optineurin-mediated-mitophagy-protects-renal-tubular-epithelial-cells-against-accelerated-senescence-in-diabetic-nephropathy
#16
Kehong Chen, Huanzi Dai, Junjie Yuan, Jia Chen, Lirong Lin, Weiwei Zhang, Limin Wang, Jianguo Zhang, Kailong Li, Yani He
Premature senescence is a key process in the progression of diabetic nephropathy (DN). Premature senescence of renal tubular epithelial cells (RTEC) in DN may result from the accumulation of damaged mitochondria. Mitophagy is the principal process that eliminates damaged mitochondria through PTEN-induced putative kinase 1 (PINK1)-mediated recruitment of optineurin (OPTN) to mitochondria. We aimed to examine the involvement of OPTN in mitophagy regulation of cellular senescence in RTEC in the context of DN. In vitro, the expression of senescence markers P16, P21, DcR2, SA-β-gal, SAHF, and insufficient mitophagic degradation marker (mitochondrial P62) in mouse RTECs increased after culture in 30 mM high-glucose (HG) conditions for 48 h...
January 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29361670/podocyte-specific-knockin-of-pten-protects-kidney-from-hyperglycemia
#17
Huizhen Wang, Ziwei Feng, Jianteng Xie, Feng Wen, Menglei Jv, Tiantian Liang, Jing Li, Yanhui Wang, Yangyang Zuo, Sheng Li, Ruizhao Li, Zhilian Li, Bin Zhang, Xinling Liang, Shuangxin Liu, Wei Shi, Wenjian Wang
Aim Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has been proved to be downregulated in podocytes challenged with high glucose (HG), and knockout of PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD). However, whether podocyte-specific knockin of PTEN protects the kidney against hyperglycemia in vivo remains undefined. Methods The inducible podocyte-specific PTEN knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop-loxP-PTEN mice with podocin-iCreERT2 mice...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29361668/cutaneous-exposure-to-lewisite-causes-acute-kidney-injury-by-invoking-dna-damage-and-autophagic-response
#18
Ritesh Srivastava, Amie M Traylor, Changzhao Li, Wenguang Feng, Lingling Guo, Veena B Antony, Trenton R Schoeb, Anupam Agarwal, Mohammad Athar
Lewisite (2-chlorovinyldichloroarsine) is an organic and arsenical chemical warfare agent which was developed and weaponized during World Wars I/II. Stockpiles of lewisite still exist in many parts of the world and pose potential environmental and human health threat. Exposure to lewisite and similar chemicals causes intense cutaneous inflammatory response. However, morbidity and mortality in the exposed population is not only due to cutaneous damage but is also a result of systemic injury. Here, we provide data delineating the pathogenesis of acute kidney injury (AKI) following cutaneous exposure to lewisite and its analogue phenylarsine oxide (PAO) in a murine model...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29358506/blockade-of-histone-deacetylase-6-protects-against-cisplatin-induced-acute-kidney-injury
#19
Jinhua Tang, Yingfeng Shi, Na Liu, Liuqing Xu, Xiujuan Zang, Peibin Li, Juanlian Zhang, Xiaoqing Zheng, Andong Qiu, Shougang Zhuang
Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs to an inorganic platinum-fundamental chemotherapeutic drug utilized in the therapy of various solid malignant tumors. However, the use of cisplatin is limited by obvious side effects. In this study, we utilized a murine model of cisplatin-induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6, tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its associated mechanisms...
January 22, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29348484/activation-of-ca2-sensing-receptor-as-a-protective-pathway-to-reduce-cadmium-induced-cytotoxicity-in-renal-proximal-tubular-cells
#20
Jie Gu, Shuya Dai, Yanmin Liu, Haitao Liu, Yao Zhang, Xingqi Ji, Feng Yu, Yang Zhou, Liang Chen, William Ka Fai Tse, Chris Kong Chu Wong, Binghai Chen, Haifeng Shi
Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce renal injury. Previous studies have proved that Cd impact on renal cell proliferation, autophagy and apoptosis, but the detoxification drugs and the functional mechanism are still in study. In this study, we used mouse renal tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling pathways. Moreover, we proposed to elucidate the prevent effect of activation of Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity and underlying mechanisms...
January 18, 2018: Scientific Reports
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