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https://www.readbyqxmd.com/read/28428331/a-personalized-model-of-coq2-nephropathy-rescued-by-the-wild-type-coq2-allele-or-dietary-coenzyme-q10-supplementation
#1
Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhanzheng Zhao, Patricio E Ray, Zhe Han
Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function...
April 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28424210/ucp2-attenuates-apoptosis-of-tubular-epithelial-cells-in-renal-ischemia-reperfusion-injury
#2
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
#3
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
#4
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/28417246/mammalian-target-of-rapamycin-mtor-as-a-potential-therapeutic-target-in-various-diseases
#5
REVIEW
Avileen Kaur, Saurabh Sharma
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that belongs to Phosphatidylinositol-3-kinase related kinase superfamily. The signaling pathways of mTOR are integrated through the protein complexes of mTORC1 and mTORC2. mTORC1 controls protein synthesis, cell growth, proliferation, autophagy, cell metabolism, and stress responses, whereas mTORC2 seems to regulate cell survival and polarity. Dysregulation of the mTOR pathway has been implicated in the pathophysiology of a number of disease conditions, including cancer, cardiovascular, neurodegenerative, and various renal diseases...
April 17, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28409163/pgc1%C3%AE-activators-mitigate-diabetic-tubulopathy-by-improving-mitochondrial-dynamics-and-quality-control
#6
So-Young Lee, Jun Mo Kang, Dong-Jin Kim, Seon Hwa Park, Hye Yun Jeong, Yu Ho Lee, Yang Gyun Kim, Dong Ho Yang, Sang Ho Lee
Purpose. In this study, we investigated the effect of PGC1α activators on mitochondrial fusion, fission, and autophagic quality control in renal tubular cells in a diabetic environment in vivo and in vitro. We also examined whether the upregulation of PGC1α attenuates diabetic tubulopathy by normalizing mitochondrial homeostasis. Methods. HKC8 cells were subjected to high-glucose conditions (30 mM D-glucose). Diabetes was induced with streptozotocin (STZ, 50 mg/kg i.p. for 5 days) in male C57/BL6J mice...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28408883/alisol-a-24-acetate-and-alisol-b-23-acetate-induced-autophagy-mediates-apoptosis-and-nephrotoxicity-in-human-renal-proximal-tubular-cells
#7
Chunfei Wang, Liang Feng, Liang Ma, Haifeng Chen, Xiaobin Tan, Xuefeng Hou, Jie Song, Li Cui, Dan Liu, Juan Chen, Nan Yang, Jing Wang, Ying Liu, Bingjie Zhao, Gang Wang, Yuanli Zhou, Xiaobin Jia
Two natural compounds alisol A 24-acetate (24A) and alisol B 23-acetate (23B) are abundant in Rhizoma alismatis. In the present study, we evaluated the induction of 24A and 23B on apoptosis and possible nephrotoxicity of human renal proximal tubular (HK-2) cells by activating autophagy and also explored its regulation on PI3K/Akt/mTOR signaling pathway. Presently, Clusterin, Kim-1, and TFF-3 were considered to be new bioindicators of nephrotoxicity. Interestingly, the protein expression and mRNA levels of Clusterin, Kim-1 and TFF-3 could be significantly increased by 23B and 24A in vivo and in vitro...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28407874/autophagy-and-renal-epithelial-transport-eat-to-survive
#8
Ewout J Hoorn, David Severs
Autophagy is an adaptive cellular response to "stress" in which proteins are targeted for lysosomal degradation. Using a combined proteomics and microscopy approach, Khositseth et al. show that autophagy contributes to the downregulation of the water channel aquaporin-2 in response to hypercalcemia. This commentary discusses the role of autophagy in renal epithelial transport, and explores whether autophagy may also contribute to chronic kidney disease once it becomes dysfunctional.
May 2017: Kidney International
https://www.readbyqxmd.com/read/28407045/novel-pathogenesis-regulation-of-apoptosis-by-apelin-apj-system
#9
Jiaqi Liu, Meiqing Liu, Linxi Chen
Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases...
April 12, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28405603/mtor-inhibition-by-everolimus-does-not-impair-closure-of-punch-biopsy-wounds-in-renal-transplant-patients
#10
Shelley B Dutt, Josephine Gonzales, Megan Boyett, Anne Costanzo, Peggy P Han, Steven Steinberg, Dianne B McKay, Julie M Jameson
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are approved to prevent allograft rejection and control malignancy. Unfortunately, they are associated with adverse effects, such as wound healing complications that detract from more extensive use. There is a lack of prospective wound healing studies to monitor patients treated with mTOR inhibitors, such as everolimus or sirolimus, especially in nondiabetics. METHODS: Patients receiving everolimus with standard immunosuppressant therapy or standard immunosuppressant therapy without everolimus were administered 3-mm skin biopsy punch wounds in the left scapular region...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28388958/pre-incubation-with-hucmsc-exosomes-prevents-cisplatin-induced-nephrotoxicity-by-activating-autophagy
#11
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
#12
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/28339082/effects-of-autophagy-and-endocytosis-on-the-activity-of-matrix-metalloproteinase%C3%A2-2-in-human-renal-proximal-tubular-cells-under-hypoxia
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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