title: Autophagy and apoptosis in tubular cells following unilateral ureteral             obstruction are associated with mitochondrial oxidative stress.
abstract: Tubular epithelial loss has been shown to be responsible for the formation             of atubular glomeruli leading to nephron decomposition and interstitial fibrosis             in obstructive uropathy. Cells undergoing apoptosis and autophagic cell death             play an important role in this process, yet the mechanisms are not fully understood.             In this study, we aimed to investigate whether autophagy cooperating with apoptosis             is associated with mitochondrial damage and whether oxidative stress plays an             important role in the loss of tubular epithelium following unilateral ureteral             obstruction. In this model, we demonstrated that there is coexistence of autophagy             and apoptosis with tubular atrophy in obstructed proximal tubules. After unilateral             ureteral obstruction (UUO), autophagy in proximal tubular cells was enhanced steadily             up to 7 days in the obstructed kidney and declined thereafter, while apoptosis             was induced in a time-dependent manner from 3 to 14 days. Mitochondrial structure             and number also changed during UUO. Lipid peroxidation products, NOX4, and NADPH             oxidase activity were also increased in the obstructed renal cortex, and peaked             at 7 days. In vitro, we showed that H2O2 induced mitochondrial injury leading             to autophagy and apoptosis through the Beclin 1 pathway and interference with             Bcl-2 expression. Thus, our data demonstrate that oxidative stress leading to             mitochondrial damage and driven autophagy-dependent cell death and apoptosis are             important mechanisms of tubular decomposition in obstructive nephropathy.
authors: Department of Nephrology, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, PR China. xuyanfang99@hotmail.com
authors: Yanfang
authors: Y
authors: Xu
authors: Shiwei
authors: S
authors: Ruan
authors: Xiaonan
authors: X
authors: Wu
authors: Hong
authors: H
authors: Chen
authors: Ke
authors: K
authors: Zheng
authors: Binbin
authors: B
authors: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D004789:Enzyme Activation; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D009399:Nephrons / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D006861:Hydrogen Peroxide; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat