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https://www.readbyqxmd.com/read/28339082/effects-of-autophagy-and-endocytosis-on-the-activity-of-matrix-metalloproteinase%C3%A2-2-in-human-renal-proximal-tubular-cells-under-hypoxia
#1
Wenmin Yu, Zhi Wang, Yiping Li, Lei Liu, Jing Liu, Fenggan Ding, Xiaoyi Zhang, Zhengyuan Cheng, Pingsheng Chen
Tubulointerstitial fibrosis is characterized by tubular atrophy with basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). A decrease in the activity of matrix metalloproteinase‑2 (MMP‑2) may promote this process. Although proximal tubular cells are sensitive to oxygen deprivation, whether cellular autophagy or endocytosis induced by hypoxia can alter the activity of MMP‑2 remains to be elucidated. The aim of the present study was to investigate whether autophagy and endocytosis induced by hypoxia can have an effect on the activity of MMP‑2 in HK‑2 cells...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#2
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28294175/the-age-associated-loss-of-ischemic-preconditioning-in-the-kidney-is-accompanied-by-mitochondrial-dysfunction-increased-protein-acetylation-and-decreased-autophagy
#3
Stanislovas S Jankauskas, Irina B Pevzner, Nadezda V Andrianova, Ljubava D Zorova, Vasily A Popkov, Denis N Silachev, Nataliya G Kolosova, Egor Y Plotnikov, Dmitry B Zorov
In young rats, ischemic preconditioning (IPC), which consists of 4 cycles of ischemia and reperfusion alleviated kidney injury caused by 40-min ischemia. However,old rats lost their ability to protect the ischemic kidney by IPC. A similar aged phenotype was demonstrated in 6-month-old OXYS rats having signs of premature aging. In the kidney of old and OXYS rats, the levels of acetylated nuclear proteins were higher than in young rats, however, unlike in young rats, acetylation levels in old and OXYS rats were further increased after IPC...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274318/-knockdown-of-atg5-enhances-the-sensitivity-of-human-renal-carcinoma-cells-to-sunitinib
#4
Peng Li, Qi Han, Ming Tang, Keqin Zhang
Objective To investigate the expression levels of autophagy-related gene 5 (ATG5) and microtubule-associated protein 1 light chain 3 (LC3) and their effects on sunitinib resistance in human renal carcinoma cells. Methods After clinic-pathologic feature and survival analysis, 99 renal clear cell carcinoma tissues with different histological grades were used to detect the expression of ATG5 and LC3 by immunohistochemistry. Renal carcinoma cell line A-498 was infected with lentivirus-mediated ATG5 shRNA. Western blot analysis was performed to confirm the efficiency of ATG5 knockdown...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28265848/apol1-and-the-immune-response-of-patients-with-systemic-lupus-erythematosus
#5
REVIEW
Ashira D Blazer, Robert M Clancy
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) confers up to a 50-fold increased risk of cardiovascular disease (CVD), and African Americans with SLE experience accelerated damage accrual and doubled cardiovascular risk when compared to their European American counterparts. RECENT FINDINGS: Genome-wide association studies have identified a substantial signal at 22q13, now assigned to variation at apolipoprotein L1 (APOL1), which has associated with progressive nondiabetic nephropathy, cardiovascular disease, and many immune-associated renal diseases, including lupus nephritis...
March 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28252052/rhein-inhibits-autophagy-in-rat-renal-tubular-cells-by-regulation-of-ampk-mtor-signaling
#6
Yue Tu, Liubao Gu, Diping Chen, Wei Wu, Hong Liu, Hao Hu, Yigang Wan, Wei Sun
Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246295/autophagy-inhibits-the-accumulation-of-advanced-glycation-end-products-by-promoting-lysosomal-biogenesis-and-function-in-the-kidney-proximal-tubules
#7
Atsushi Takahashi, Yoshitsugu Takabatake, Tomonori Kimura, Ikuko Maejima, Tomoko Namba, Takeshi Yamamoto, Jun Matsuda, Satoshi Minami, Jun-Ya Kaimori, Isao Matsui, Taiji Matsusaka, Fumio Niimura, Tamotsu Yoshimori, Yoshitaka Isaka
Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system which regulates intracellular homeostasis by engulfing cytoplasmic components. We have recently demonstrated that autophagic degradation of damaged lysosomes is indispensable for cellular homeostasis in some settings...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28243190/maternal-l-carnitine-supplementation-improves-brain-health-in-offspring-from-cigarette-smoke-exposed-mothers
#8
Yik Lung Chan, Sonia Saad, Ibrahim Al-Odat, Brian G Oliver, Carol Pollock, Nicole M Jones, Hui Chen
Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the brain is unknown. Here, we investigated the effects of maternal L-Carnitine supplementation on brain markers of oxidative stress, autophagy, mitophagy and mitochondrial energy producing oxidative phosphorylation (OXPHOS) complexes in SE offspring...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28236091/viability-of-primary-cultured-podocytes-is-associated-with-extracellular-high-glucose-dependent-autophagy-downregulation
#9
Irena Audzeyenka, Dorota Rogacka, Agnieszka Piwkowska, Stefan Angielski, Maciej Jankowski
Structural and functional impairment of podocytes plays an important role in the development of diabetic nephropathy, a chronic complication of diabetes mellitus and leading cause of renal failure requiring renal replacement therapy. Autophagy plays a crucial role in podocyte viability and function, and its activity is modulated by a variety of pathophysiological factors found in diabetic milieu. Here we show that downregulation of autophagy is critical for podocyte survival in hyperglycemic environment. Moreover, long-term exposure to high glucose leads to inhibition of autophagy as well as to the development of insulin resistance in podocytes...
February 24, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28205545/octreotide-attenuates-acute-kidney-injury-after-hepatic-ischemia-and-reperfusion-by-enhancing-autophagy
#10
Huiping Sun, Shuangfa Zou, Keith A Candiotti, Yanhua Peng, Qinya Zhang, Weiqiang Xiao, Yiyun Wen, Jiao Wu, Jinfeng Yang
Octreotide exerts a protective effect in hepatic ischemia-reperfusion (HIR) injury. However, whether octreotide preconditioning could also reduce acute kidney injury (AKI) after HIR is unknown. This study was designed to investigate the role of octreotide in AKI after HIR. Male Sprague-Dawley rats were pretreated with octreotide or octreotide combined with 3-methyladenine (autophagy inhibitor, 3MA). Plasma creatinine, inflammation markers (e.g., TNF-α and IL-6 etc.), apoptosis, autophagy and phosphorylation of protein kinase B/mammalian target of rapamycin/p70 ribosomal S6 kinase (Akt/mTOR/p70S6K) in the kidney were measured after 60 minutes of liver ischemia and 24 hours of reperfusion for each rat...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28184034/hyperbaric-oxygenation-protects-against-ischemia-reperfusion-injury-in-transplanted-rat-kidneys-by-triggering-autophagy-and-inhibiting-inflammatory-response
#11
Ding-Su Bao, Yu-Ke Wu, Shi-Jie Fu, Guo-You Wang, Si-Jin Yang, Guo-Biao Liang, Zhi-Hui Xie, Song Rong
BACKGROUND Ischemia-reperfusion injury (IRI) is a clinically common pathologic process defined as the inability to improve neuronal function. This study aimed to investigate the pathological mechanism of IRI and to explore effects of hyperbaric oxygenation (HBO) on autophagy and inflammatory response in IRI. MATERIAL AND METHODS Ninety Sprague-Dawley (SD) rats were randomly divided into a Sham group, a kidney transplant group (Trans), and a kidney transplant plus HBO treatment group (Trans+HBO). The kidney was harvested from the donor and transplanted to recipient rats according to a previously reported study...
February 10, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/28182710/tangshen-formula-attenuates-diabetic-renal-injuries-by-upregulating-autophagy-via-inhibition-of-plzf-expression
#12
Hailing Zhao, Xin Li, Tingting Zhao, Haojun Zhang, Meihua Yan, Xi Dong, Pengmin Chen, Liang Ma, Ping Li
The Chinese herbal granule Tangshen Formula (TSF) has been proven to decrease proteinuria and improve estimated glomerular filtration rate (eGFR) in diabetic kidney disease (DKD) patients. However, the underlying mechanism of TSF on treatment of diabetic nephropathy (DN) remains unclear. The present study aimed to identify the therapeutic target of TSF in diabetic renal injuries through microarray-based gene expression profiling and establish its underlying mechanism. TSF treatment significantly attenuated diabetic renal injuries by inhibiting urinary excretion of albumin and renal histological injuries in diabetic (db/db) mice...
2017: PloS One
https://www.readbyqxmd.com/read/28165842/stagnation-of-autophagy-a-novel-mechanism-of-renal-lipotoxicity
#13
Yoshitsugu Takabatake, Takeshi Yamamoto, Yoshitaka Isaka
Excessive fat intake can lead to cellular injury and inflammation (termed lipotoxicity), but studies on lipid metabolism in the kidney have been scarce. We recently identified a novel mechanism of lipotoxicity in the kidney proximal tubules especially focusing on the effect of lipid overload on lysosomal function and autophagic activity. Lipid overload basically stimulates macroautophagy/autophagy for renovation of the plasma and organelle membranes, which plays an essential role in maintaining the integrity of proximal tubules...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28158902/metformin-attenuates-albumin-induced-alterations-in-renal-tubular-cells-in-vitro
#14
Soumaya Allouch, Shankar Munusamy
Proteinuria (albuminuria) plays a crucial role in the etiology of chronic kidney disease (CKD) via alteration of multiple signaling pathways and cellular process in renal cells. The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28139295/hypercalcemia-induces-targeted-autophagic-degradation-of-aquaporin-2-at-the-onset-of-nephrogenic-diabetes-insipidus
#15
Sookkasem Khositseth, Komgrid Charngkaew, Chatikorn Boonkrai, Poorichaya Somparn, Panapat Uawithya, Nusara Chomanee, D Michael Payne, Robert A Fenton, Trairak Pisitkun
Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased...
January 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28134775/chrysin-protects-rat-kidney-from-paracetamol-induced-oxidative-stress-inflammation-apoptosis-and-autophagy-a-multi-biomarker-approach
#16
Fatih Mehmet Kandemir, Sefa Kucukler, Eyup Eldutar, Cuneyt Caglayan, İlhami Gülçin
Paracetamol (PC) is a safe analgesic and antipyretic drug at therapeutic doses, and it is widely used in clinics. However, at high doses, it can induce hepatotoxicity and nephrotoxicity. Chrysin (CR) is a natural flavonoid that has biological activities that include being an antioxidant, an anti-inflammatory, and an anti-cancer agent. The main objective of this study was to investigate the efficacy of CR against PC-induced nephrotoxicity in rats. CR was given orally via feeding needle to male Sprague Dawley rats as a single daily dose of 25 or 50 mg/kg for six days...
January 26, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28118075/dietary-spermidine-for-lowering-high-blood-pressure
#17
Tobias Eisenberg, Mahmoud Abdellatif, Andreas Zimmermann, Sabrina Schroeder, Tobias Pendl, Alexandra Harger, Slaven Stekovic, Julia Schipke, Christoph Magnes, Albrecht Schmidt, Christoph Ruckenstuhl, Christopher Dammbrueck, Angelina S Gross, Viktoria Herbst, Didac Carmona-Gutierrez, Federico Pietrocola, Thomas R Pieber, Stephan J Sigrist, Wolfgang A Linke, Christian Mühlfeld, Junichi Sadoshima, Joern Dengjel, Stefan Kiechl, Guido Kroemer, Simon Sedej, Frank Madeo
Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure...
January 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28118053/drain-the-lysosome-development-of-the-novel-orally-available-autophagy-inhibitor-roc-325
#18
Jennifer S Carew, Steffan T Nawrocki
Although macroautophagy/autophagy is a key contributor to malignant pathogenesis and therapeutic resistance, there are few FDA-approved agents that significantly affect this pathway. We used medicinal chemistry strategies to develop ROC-325, an orally available novel inhibitor of lysosomal-mediated autophagy. Detailed in vitro and in vivo studies in preclinical models of renal cell carcinoma demonstrated that ROC-325 triggered the hallmark features of lysosomal autophagy inhibition, was very well tolerated, and exhibited significant superiority with respect to autophagy inhibition and anticancer activity over hydroxychloroquine...
January 24, 2017: Autophagy
https://www.readbyqxmd.com/read/28112877/autophagy-in-renal-tubular-injury-and-repair
#19
REVIEW
Fangming Lin
Autophagy is a fundamental cellular process that maintains normal function and structure of the cell. It can be induced during stress and serves as an adaptive response for cell survival. Normal kidneys have high metabolic demands yet are relatively hypoxic, especially in the medulla and papilla. Injury or aging aggravates metabolic perturbation and activates autophagy in many types of renal cells. In the kidney, tubular epithelial cells consume the most energy due to active transport mechanisms and therefore are the most susceptible to injuries from hypoxic or low energy states...
January 23, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28055301/autophagy-orchestrates-adaptive-responses-to-targeted-therapy-in-endometrial-cancer
#20
Núria Eritja, Bo-Juen Chen, Ruth Rodríguez-Barrueco, Maria Santacana, Sònia Gatius, August Vidal, Maria Dolores Martí, Jordi Ponce, Laura Bergadà, Andree Yeramian, Mario Encinas, Joan Ribera, Jaume Reventós, Jeff Boyd, Alberto Villanueva, Xavier Matias-Guiu, Xavier Dolcet, David Llobet-Navàs
Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma...
March 4, 2017: Autophagy
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