Splice variants of neuronal nitric oxide synthase are present in the rat kidney

Smith, Cheryl A.; Merchant, Michael L.; Fekete, Andrea; Nyugen, Ha-Long; Oh, Paul; Tain, You‐Lin; Klein, Jon B.; Baylis, Chris

doi:10.1093/ndt/gfn676

Cited by 43 publications

(51 citation statements)

References 22 publications

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“…Similar results were reported in rat kidney and brain (26). PI3K (~85 kDa), Akt (~60 kDa), and their phosphorylated forms exist in antral mucosa and MKN28 cells (a cell line of human gastric cancer) (Fig.…”

Section: Phosphorylation Of Pi3k Akt and Nos1 Stimulated By Pparα Isupporting

confidence: 87%

PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca2+-regulated exocytosis

et al. 2016

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A PPARα (peroxisome proliferation activation receptor α) agonist (GW7647) activates nitric oxide synthase 1 (NOS1) to produce NO leading to cGMP accumulation in antral mucous cells. In this study, we examined how PPARα activates NOS1. The NO production stimulated by GW7647 was suppressed by inhibitors of PI3K (wortmannin) and Akt (AKT 1/2 Kinase Inhibitor, AKT-inh), although it was also suppressed by the inhibitors of PPARα (GW6471) and NOS1 (N-PLA). GW7647 enhanced the ACh (acetylcholine)-stimulated exocytosis (Ca 2+

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Section: Phosphorylation Of Pi3k Akt and Nos1 Stimulated By Pparα Isupporting

confidence: 87%

PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca2+-regulated exocytosis

et al. 2016

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“…There are multiple splice variants of nNOS (5), and, in the rat kidney, in addition to the full-length ϳ160-kDa nNOS␣ protein, we find nNOS␤, at both the transcript and protein level (110). The nNOS␤ transcript is an exon 2 deletion which encodes a ϳ140-kDa nNOS protein that is an active enzyme and which lacks the unique NH 2 terminus of the nNOS␣ (5).…”

Section: Renal No Productionmentioning

confidence: 88%

Nitric oxide deficiency in chronic kidney disease

Baylis

2008

American Journal of Physiology-Renal Physiology

353

322

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The overall production of nitric oxide (NO) is decreased in chronic kidney disease (CKD) which contributes to cardiovascular events and further progression of kidney damage. There are many likely causes of NO deficiency in CKD and the areas surveyed in this review are: 1. Limitations on substrate (l-Arginine) availability, probably due to impaired renal l-Arginine biosynthesis, decreased transport of l-Arginine into endothelial cells and possible competition between NOS and competing metabolic pathways, such as arginase. 2. Increased circulating levels of endogenous NO synthase (NOS) inhibitors, in particular asymmetric dimethylarginine (ADMA). Increased methylation of proteins and their subsequent breakdown to release free ADMA may contribute but the major culprit is probably reduced ADMA catabolism by the enzymes dimethylarginine dimethylaminohydrolases. 3. Reduced renal cortex abundance of the neuronal NOS (nNOS)α protein correlates with injury while increasing nNOSβ abundance may provide a compensatory, protective response. Interventions that can restore NO production by targeting these various pathways are likely to reduce the cardiovascular complications of CKD as well as slowing the rate of progression.

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“…Likewise, Sun et al showed that glomerular endothelial dysfunction and damage precede podocyte damage in ADR-induced nephropathy in C57BL/6 mice with eNOS defi ciency [11], indicating the importance of glomerular endothelial cells in the pathogenesis of proteinuria and development of glomerulosclerosis, tubulointerstitial fi brosis and infl ammation. Furthermore, the reduction in nNOS protein abundance correlates with increasing glomerular damage and decreasing renal function in different animal models of CKD [13,27,28], suggesting that the renal nNOS response to kidney damage may be an important determinant of the susceptibility to CKD progression.…”

Section: Discussionmentioning

confidence: 99%

Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

et al. 2017

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Down-regulation of nitric oxide synthase (NOS) and NO defi ciency in the kidneys have been implicated in the pathogenesis of chronic kidney disease (CKD). In this study we examined the effects of losartan, tempol, and combined treatment on three NOS isoforms expressions, kidney NO content and NOS correlation with renal function and structure in the early stage of adriamycin (ADR)-induced CKD in spontaneously hypertensive rats (SHR). Rats were divided into control group, and four other groups which were treated with ADR and received vehicle, losartan (L, angiotensin II type 1 receptor blocker), tempol (T, redox-cycling nitroxide) or T+L treatment (by gavage) in a six-week study. Reduction of all NOS isoforms expressions were signifi cantly improved by losartan or tempol, and correlated with proteinuria amelioration. Combined treatment induced down-regulation of constitutive NOS isoforms, whilst inducible NOS was up-regulated and followed by increased nitrite content and a signifi cant decline in the glomerular fi ltration rate. Losartan or tempol prevented ADR-induced neoexpression of vimentin in the glomeruli and tubulointerstital areas, whereas de novo vimentin expression was still observed in the atrophic tubules and in the interstitial fi broblasts and myofi broblasts in combined treatment. It can be concluded that single treatments, contrary to combined, were effective in improving NO bioavailability and slowing down the progression of CKD.

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Splice variants of neuronal nitric oxide synthase are present in the rat kidney

Abstract: The renal cortical nNOSbeta protein is present in low abundance in the normal kidney and increases with injury, in an inverse pattern of change with the nNOSalpha.

Cited by 43 publications

References 22 publications

<b>PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca</b><sup><b>2+</b></sup><b>-regulated </b><b>exocytosis </b>

<b>PPARα induced NOS1 phosphorylation via PI3K/Akt in guinea pig antral mucous cells: NO-enhancement in Ca</b><sup><b>2+</b></sup><b>-regulated </b><b>exocytosis </b>

Nitric oxide deficiency in chronic kidney disease

Effects of Losartan, Tempol, and Their Combination On Renal Nitric Oxide Synthases in the Animal Model of Chronic Kidney Disease

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