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https://www.readbyqxmd.com/read/28424210/ucp2-attenuates-apoptosis-of-tubular-epithelial-cells-in-renal-ischemia-reperfusion-injury
#1
Yang Zhou, Ting Cai, Jing Xu, Lei Jiang, Jining Wu, Qi Sun, Ke Zen, Junwei Yang
Uncoupling protein 2 (UCP2) plays critical roles in energy metabolism and cell survival. Previous investigations showed that UCP2 regulated the production of extracellular matrix and renal fibrosis. However, little is known about UCP2 in acute kidney injury. Here, we used UCP2 knockout mice to investigate the role of UCP2 in AKI model generated by renal ischemia/reperfusion (I/R) injury. The UCP2 global knockout mice were born and growth normal without kidney histological abnormality or renal dysfunctions. As compared with littermates, deletion of UCP2 exacerbated I/R-induced AKI while increase of UCP2 by conjugated linoleic acid (CLA) attenuated I/R injury...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28423497/drp1-dependent-mitophagy-protects-against-cisplatin-induced-apoptosis-of-renal-tubular-epithelial-cells-by-improving-mitochondrial-function
#2
Chuanyan Zhao, Zhuyun Chen, Jia Qi, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Ming Zeng, Bo Zhang, Ningning Wang, Huijuan Mao, Aihua Zhang, Changying Xing, Yanggang Yuan
Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417340/preconditioning-of-primary-human-renal-proximal-tubular-epithelial-cells-without-tryptophan-increases-survival-under-hypoxia-by-inducing-autophagy
#3
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Nikolaos Antoniadis, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Hypoxia plays a significant role in the pathogenesis of acute kidney injury (AKI). Autophagy protects from AKI. Amino acid deprivation induces autophagy. The effect of L-tryptophan depletion on survival and autophagy in cultures of renal proximal tubular epithelial cells (RPTECs) under hypoxia was evaluated. METHODS: RPTECs were preconditioned in a medium containing or not tryptophan, following culture under hypoxia and treatment with or without the autophagy inhibitor chloroquine...
April 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28388958/pre-incubation-with-hucmsc-exosomes-prevents-cisplatin-induced-nephrotoxicity-by-activating-autophagy
#4
Bingying Wang, Haoyuan Jia, Bin Zhang, Juanjuan Wang, Cheng Ji, Xueming Zhu, Yongmin Yan, Lei Yin, Jing Yu, Hui Qian, Wenrong Xu
BACKGROUND: The administration of cisplatin is limited due to its nephrotoxic side effects, and prevention of this nephrotoxicity of cisplatin is difficult. Mesenchymal stem cell (MSC)-derived exosomes have been implicated as a novel therapeutic approach for tissue injury. In this study, we demonstrated that the pretreatment of human umbilical cord MSC-derived exosomes (hucMSC-Ex) can prevent the development of cisplatin-induced renal toxicity by activation of autophagy in vitro and in vivo...
April 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28367814/-autophagy-in-the-kidney
#5
Nicolas Pallet
Autophagy is a highly conserved, physiological, catabolic process, involving the lysosomal degradation of cytosolic components, including macromolecules (such as proteins and lipids) and cytosolic organelles. Autophagy is believed to be essential for the maintenance of cellular homeostasis, for a number of fundamental biological activities, and an important component of the complex response of cells to multiple forms of stress. Autophagy is involved in the pathogenesis of a number of clinically important disorders but, until recently, little was known about its connection to kidney diseases...
March 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28205545/octreotide-attenuates-acute-kidney-injury-after-hepatic-ischemia-and-reperfusion-by-enhancing-autophagy
#6
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/28139396/heme-oxygenase-1-as-a-therapeutic-target-in-acute-kidney-injury
#7
Subhashini Bolisetty, Abolfazl Zarjou, Anupam Agarwal
A common clinical condition, acute kidney injury (AKI) significantly influences morbidity and mortality, particularly in critically ill patients. The pathophysiology of AKI is complex and involves multiple pathways, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Recent evidence suggests that a single insult to the kidney significantly enhances the propensity to develop chronic kidney disease. Therefore, the generation of effective therapies against AKI is timely. In this context, the cytoprotective effects of heme oxygenase 1 (HO-1) in animal models of AKI are well documented...
April 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28003091/recycling-to-discover-something-new-the-role-of-autophagy-in-kidney%C3%A2-disease
#8
Jeremy S Leventhal, Christina M Wyatt, Michael J Ross
This year, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his groundbreaking work in dissecting the mechanisms of autophagy, a cellular process resulting in the organized degradation of cytoplasmic components. Ohsumi's work paved the way for subsequent studies that demonstrated critical roles for autophagy in modulating both acute and chronic kidney injury. This work may lead to future therapeutic approaches that target the autophagy system to prevent or treat kidney diseases...
January 2017: Kidney International
https://www.readbyqxmd.com/read/27715411/the-impact-of-autophagy-on-the-development-of-senescence-in-primary-tubular-epithelial-cells
#9
Arpita Baisantry, Sagar Bhayana, Christoph Wrede, Jan Hegermann, Hermann Haller, Anette Melk, Roland Schmitt
Autophagy and senescence are 2 distinct pathways that are importantly involved in acute kidney injury and renal repair. Recent data indicate that the 2 processes might be interrelated. To investigate the potential link between autophagy and senescence in the kidney we isolated primary tubular epithelial cells (PTEC) from wild-type mice and monitored the occurrence of cellular senescence during autophagy activation and inhibition. We found that the process of cell isolation and transfer into culture was associated with a strong basal autophagic activation in PTEC...
November 2016: Cell Cycle
https://www.readbyqxmd.com/read/27498898/acute-renal-failure-a-serious-complication-in-patients-after-kidney-transplantation
#10
REVIEW
G Basta-Jovanovic, Lj Bogdanovic, M Radunovic, M Prostran, R Naumovic, S Simic-Ogrizovic, S Radojevic-Skodric
Free radical-mediated injury releases proinflammatory cytokines and activates innate immunity. It has been suggested that the early innate response and the ischemic tissue damage play roles in the development of adaptive responses, which may lead to acute kidney rejection. Various durations of hypothermic kidney storage before transplantation add to ischemic tissue damage. The final stage of ischemic injury occurs during reperfusion that develops hours or days after the initial insult. Repair and regeneration processes occur together with cellular apoptosis, autophagy and necrosis and a favorable outcome is expected if regeneration prevails...
2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27380103/neutrophil-gelatinase-associated-lipocalin-worsens-ischemia-reperfusion-damage-of-kidney-cells-by-autophagy
#11
Wenjing Zhang, Shuo Yang, Liyan Cui, Jie Zhang
This study aimed to explore the influence of neutrophil gelatinase-associated lipocalin on autophagy and its role in ischemia/reperfusion injury in human kidney-2 (HK-2) cells during acute kidney injury (AKI). HK-2 cells were given hypoxia/reoxygenation treatment for different times to simulate ischemia/reperfusion injury. Autophagy was evaluated by western blot and immunofluorescence of GFP-LC3. Cell viability was tested to reflect the degree of cell damage. The autophagy inhibitor 3-MA was used to inhibit autophagy and determine the role of autophagy in ischemia/reperfusion injury...
August 2016: Renal Failure
https://www.readbyqxmd.com/read/27376761/telomerase-autophagy-and-acute-kidney-injury
#12
Raymond C Harris, Huifang Cheng
In humans, aging is associated with telomere shortening and increased susceptibility to acute kidney injury. Telomerase is essential to maintain telomere length. The fourth generation mice with telomerase deletion have progressive shortening of telomeres. Those mice delayed recovery from ischemia-reperfusion injury, due to an increase in tubule cell senescence and impairment of autophagy, the latter of which may be mediated in part by increased mTOR signaling. © 2016 S. Karger AG, Basel.
2016: Nephron
https://www.readbyqxmd.com/read/27339388/the-role-of-bcl-2-family-members-in-acute-kidney-injury
#13
REVIEW
Steven C Borkan
B-cell lymphoma 2 (BCL-2) family proteins gather at the biologic cross-roads of renal cell survival: the outer mitochondrial membrane. Despite shared sequence and structural features, members of this conserved protein family constantly antagonize each other in a life-and-death battle. BCL-2 members innocently reside within renal cells until activated or de-activated by physiologic stresses caused by common nephrotoxins, transient ischemia, or acute glomerulonephritis. Recent experimental data not only illuminate the intricate mechanisms of apoptosis, the most familiar form of BCL-2-mediated cell death, but emphasizes their newfound roles in necrosis, necroptosis, membrane pore transition regulated necrosis, and other forms of acute cell demise...
May 2016: Seminars in Nephrology
https://www.readbyqxmd.com/read/27166518/mitochondria-as-therapeutic-targets-in-acute-kidney-injury
#14
Andrew M Hall, Claus D Schuh
PURPOSE OF REVIEW: Mitochondria are complex intracellular organelles with a variety of important functions. The kidney tubule is densely packed with mitochondria, and mitochondrial dysfunction is thought to be central to the pathogenesis of acute kidney injury (AKI). Mitochondria therefore represent potential targets for novel therapeutic interventions in AKI. RECENT FINDINGS: Several mitochondrial targeted approaches have shown promise in recent preclinical studies of AKI, including measures to: reduce oxidative stress within mitochondria; prevent mitochondrial fission and activation of cell death pathways; enhance recycling of damaged mitochondria via autophagy and mitophagy; and accelerate mitochondrial biogenesis postinsult...
July 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27153058/autophagy-innate-immunity-and-tissue-repair-in-acute-kidney-injury
#15
REVIEW
Pu Duann, Elias A Lianos, Jianjie Ma, Pei-Hui Lin
Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI) is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation...
May 3, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27140855/long-noncoding-rnas-in-kidney-and-cardiovascular-diseases
#16
REVIEW
Johan M Lorenzen, Thomas Thum
Transcription of a large part of the human genome results in RNA transcripts that have limited or no protein-coding potential. These include long noncoding RNAs (lncRNAs), which are defined as being ≥200 nucleotides long. Unlike microRNAs, which have been extensively studied, little is known about the functional role of lncRNAs. However, studies over the past 5 years have shown that lncRNAs interfere with tissue homeostasis and have a role in pathological processes, including in the kidney and heart. The developmental expression of the microRNA sponge H19, for example, is altered in the kidneys of embryos carried by hyperglycaemic mothers, and the lncRNA Malat1 regulates hyperglycaemia-induced inflammation in endothelial cells...
June 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27108948/renoprotective-approaches-and-strategies-in-acute-kidney-injury
#17
REVIEW
Yuan Yang, Meifang Song, Yu Liu, Hong Liu, Lin Sun, Youming Peng, Fuyou Liu, Manjeri A Venkatachalam, Zheng Dong
Acute kidney injury (AKI) is a major renal disease associated with high mortality rate and increasing prevalence. Decades of research have suggested numerous chemical and biological agents with beneficial effects in AKI. In addition, cell therapy and molecular targeting have been explored for reducing kidney tissue damage and promoting kidney repair or recovery from AKI. Mechanistically, these approaches may mitigate oxidative stress, inflammation, cell death, and mitochondrial and other organellar damage, or activate cytoprotective mechanisms such as autophagy and pro-survival factors...
July 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27052588/metformin-protects-against-cisplatin-induced-tubular-cell-apoptosis-and-acute-kidney-injury-via-ampk%C3%AE-regulated-autophagy-induction
#18
Jianzhong Li, Yuan Gui, Jiafa Ren, Xin Liu, Ye Feng, Zhifeng Zeng, Weichun He, Junwei Yang, Chunsun Dai
Metformin, one of the most common prescriptions for patients with type 2 diabetes, is reported to protect the kidney from gentamicin-induced nephrotoxicity. However, the role and mechanisms for metformin in preventing cisplatin-induced nephrotoxicity remains largely unknown. In this study, a single intraperitoneal injection of cisplatin was employed to induce acute kidney injury (AKI) in CD1 mice. The mice exhibited severe kidney dysfunction and histological damage at day 2 after cisplatin injection. Pretreatment of metformin could markedly attenuate cisplatin-induced acute kidney injury, tubular cell apoptosis and inflammatory cell accumulation in the kidneys...
April 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27048819/regulation-of-necrotic-cell-death-p53-parp1-and-cyclophilin-d-overlapping-pathways-of-regulated-necrosis
#19
REVIEW
Yuan Ying, Babu J Padanilam
In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined...
June 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/26990086/autophagy-limits-endotoxemic-acute-kidney-injury-and-alters-renal-tubular-epithelial-cell-cytokine-expression
#20
Jeremy S Leventhal, Jie Ni, Morgan Osmond, Kyung Lee, G Luca Gusella, Fadi Salem, Michael J Ross
Sepsis related acute kidney injury (AKI) is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC) from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS), a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling...
2016: PloS One
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