NADPH Oxidase Nox5 Aggravates Renal Injury in Akita Mouse Model of Diabetic Nephropathy

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 505-P
Author(s):  
JAY C. JHA ◽  
AOZHI DAI ◽  
MARK E. COOPER ◽  
RHIAN M. TOUYZ ◽  
CHRIS KENNEDY ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Nadph Oxidase ◽  
Renal Injury

scholarly journals NADPH Oxidase Nox5 Accelerates Renal Injury in Diabetic Nephropathy

Diabetes ◽  
2017 ◽  
Vol 66 (10) ◽  
pp. 2691-2703 ◽  
Author(s):  
Jay C. Jha ◽  
Claudine Banal ◽  
Jun Okabe ◽  
Stephen P. Gray ◽  
Thushan Hettige ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nadph Oxidase ◽  
Renal Injury

Prevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy

2004 ◽  
Vol 19 (1) ◽  
pp. 127-129 ◽  
Author(s):  
Takayoshi Suganami ◽  
Masashi Mukoyama ◽  
Kiyoshi Mori ◽  
Hideki Yokoi ◽  
Masao Koshikawa ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Renal Injury

Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy

2016 ◽  
Vol 310 (6) ◽  
pp. F547-F559 ◽  
Author(s):  
Yanjuan Hou ◽  
Shuangcheng Li ◽  
Ming Wu ◽  
Jinying Wei ◽  
Yunzhuo Ren ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Nadph Oxidase ◽  
P38 Mapk ◽  
Renal Injury ◽  
Oxidase Activity ◽  
Transforming Growth Factor ◽  
Ros Generation ◽  
Diabetic Mice ◽  
Nadph Oxidase Activity ◽  
Tgf Β1

Oxidative stress is implicated in the pathogenesis of diabetic kidney injury. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge reactive oxygen species (ROS). Here, we investigated the effect and molecular mechanism of mitochondria-targeted antioxidant peptide SS-31 on injuries in diabetic kidneys and mouse mesangial cells (MMCs) exposed to high-glucose (HG) ambience. CD-1 mice underwent uninephrectomy and streptozotocin treatment prior to receiving daily intraperitoneal injection of SS-31 for 8 wk. The diabetic mice treated with SS-31 had alleviated proteinuria, urinary 8-hydroxy-2-deoxyguanosine level, glomerular hypertrophy, and accumulation of renal fibronectin and collagen IV. SS-31 attenuated renal cell apoptosis and expression of Bax and reversed the expression of Bcl-2 in diabetic mice kidneys. Furthermore, SS-31 inhibited expression of transforming-growth factor (TGF)-β1, Nox4, and thioredoxin-interacting protein (TXNIP), as well as activation of p38 MAPK and CREB and NADPH oxidase activity in diabetic kidneys. In vitro experiments using MMCs revealed that SS-31 inhibited HG-mediated ROS generation, apoptosis, expression of cleaved caspase-3, Bax/Bcl-2 ratio, and cytochrome c (cyt c) release from mitochondria. SS-31 normalized mitochondrial potential (ΔΨm) and ATP alterations, and inhibited the expression of TGF-β1, Nox4, and TXNIP, as well as activation of p38 MAPK and CREB and NADPH oxidase activity in MMCs under HG conditions. SS-31 treatment also could reverse the reduction of thioredoxin (TRX) biologic activity and upregulate expression of thioredoxin 2 (TRX2) in MMCs under HG conditions. In conclusion, this study demonstrates a protective effect of SS-31 against HG-induced renal injury via an antioxidant mechanism in diabetic nephropathy.

scholarly journals SP276HIGH PROTEIN AGGRAVATES, AND MINERALOCORTICOID ANTAGONISM AMELIORATES RENAL INJURY IN THE BTBR OB/OB MOUSE MODEL OF DIABETIC NEPHROPATHY

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i180-i180
Author(s):  
Lena William-Olsson ◽  
Maria Wigstrand ◽  
Gina Hyberg ◽  
Ulrika Dahlqvist ◽  
Ann-Katrin Andersson ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Renal Injury

483-P: Key Biochemical and Histopathological Markers of Diabetic Nephropathy Correlate with Hypertension in the Renin-AAV Uninephrectomized db/db Mouse Model

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 483-P
Author(s):  
METTE V. ØSTERGAARD ◽  
IDA R. SØRENSEN ◽  
ANNEMARIE A. PEDERSEN ◽  
THOMAS SECHER ◽  
FREDERIKKE E. SEMBACH ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Mouse Model

Poly(ADP-ribose) polymerase-1 gene ablation protects mice from ischemic renal injury

2005 ◽  
Vol 288 (2) ◽  
pp. F387-F398 ◽  
Author(s):  
Jianfeng Zheng ◽  
Kishor Devalaraja-Narashimha ◽  
Kurinji Singaravelu ◽  
Babu J. Padanilam
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Mouse Model ◽  
Renal Injury ◽  
Atp Depletion ◽  
Inflammatory Cascade ◽  
Renal Functions ◽  
Atp Levels ◽  
Ischemic Renal Injury ◽  
Parp 1

Increased generation of reactive oxygen species (ROS) and the subsequent DNA damage and excessive activation of poly(ADP-ribose) polymerase-1 (PARP-1) have been implicated in the pathogenesis of ischemic injury. We previously demonstrated that pharmacological inhibition of PARP protects against ischemic renal injury (IRI) in rats (Martin DR, Lewington AJ, Hammerman MR, and Padanilam BJ. Am J Physiol Regul Integr Comp Physiol 279: R1834–R1840, 2000). To further define the role of PARP-1 in IRI, we tested whether genetic ablation of PARP-1 attenuates tissue injury after renal ischemia. Twenty-four hours after reperfusion following 37 min of bilateral renal pedicle occlusion, the effects of the injury on renal functions in PARP−/− and PARP+/+ mice were assessed by determining glomerular filtration rate (GFR) and the plasma levels of creatinine. The levels of plasma creatinine were decreased and GFR was augmented in PARP−/− mice. Morphological evaluation of the kidney tissues showed that the extent of damage due to the injury in PARP−/− mice was less compared with their wild-type counterparts. The levels of ROS and DNA damage were comparable in the injured kidneys of PARP+/+ and PARP−/− mice. PARP activity was induced in ischemic kidneys of PARP+/+ mice at 6–24 h postinjury. At 6, 12, and 24 h after injury, ATP levels in the PARP+/+ mice kidney declined to 28, 26, and 43%, respectively, whereas it was preserved close to normal levels in PARP−/− mice. The inflammatory cascade was attenuated in PARP−/− mice as evidenced by decreased neutrophil infiltration and attenuated expression of inflammatory molecules such as TNF-α, IL-1β, and intercellular adhesion molecule-1. At 12 h postinjury, no apoptotic cell death was observed in PARP−/− mice kidneys. However, by 24 h postinjury, a comparable number of cells underwent apoptosis in both PARP−/− and PARP+/+ mice kidneys. Thus activation of PARP post-IRI contributes to cell death most likely by ATP depletion and augmentation of the inflammatory cascade in the mouse model. PARP ablation preserved ATP levels, renal functions, and attenuated inflammatory response in the setting of IRI in the mouse model. PARP inhibition may have clinical efficacy in preventing the progression of acute renal failure complications.

Diabetic kidney disease in thedb/dbmouse

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mouse Model ◽  
Renal Disease ◽  
Mouse Models ◽  
Diabetic Kidney Disease ◽  
Diabetic Kidney ◽  
Matrix Expansion ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.

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