Hsp90β is involved in the development of high salt-diet-induced nephropathy via interaction with various signalling proteins

A high-salt diet often leads to a local intrarenal increase in renal hypoxia and oxidative stress, which are responsible for an excess production of pathogenic substances. Here, Wistar Kyoto/spontaneous hypertensive (WKY/SHR) rats fed a high-salt diet developed severe proteinuria, resulting from pronounced renal inflammation, fibrosis and tubular epithelial cell apoptosis. All these were mainly non-pressure-related effects. Hsp90β, TGF-β, HIF-1α, TNF-α, IL-6 and MCP-1 were shown to be highly expressed in response to salt loading. Next, we found that Hsp90β might play the key role in non-pressure-related effects of salt loading through a series of cellular signalling events, including the NF-κB, p38 activation and Bcl-2 inactivation. Hsp90β was previously proven to regulate the upstream mediators in multiple cellular signalling cascades through stabilizing and maintaining their activities. In our study, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) or Hsp90β knockdown dramatically alleviated the high-salt-diet-induced proteinuria and renal damage without altering blood pressure significantly, when it reversed activations of NF-κB, mTOR and p38 signalling cascades. Meanwhile, Co-IP results demonstrated that Hsp90β could interact with and stabilize TAK1, AMPKα, IKKα/β, HIF-1α and Raptor, whereas Hsp90β inhibition disrupted this process. In addition, Hsp90β inhibition-mediated renal improvements also accompanied the reduction of renal oxidative stress. In conclusion, salt loading indeed exhibited non-pressure-related impacts on proteinuria and renal dysfunction in WKY/SHR rats. Hsp90β inhibition caused the destabilization of upstream mediators in various pathogenic signalling events, thereby effectively ameliorating this nephropathy owing to renal hypoxia and oxidative stress.

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Helicobacter pylori AdaptationIn Vivoin Response to a High-Salt Diet

Infection and Immunity ◽

10.1128/iai.00918-15 ◽

2015 ◽

Vol 83 (12) ◽

pp. 4871-4883 ◽

Cited By ~ 11

Author(s):

John T. Loh ◽

Jennifer A. Gaddy ◽

Holly M. Scott Algood ◽

Silvana Gaudieri ◽

Simon Mallal ◽

...

Keyword(s):

Oxidative Stress ◽

Helicobacter Pylori ◽

High Salt ◽

Mongolian Gerbils ◽

High Salt Diet ◽

Salt Diet ◽

Content Type ◽

Regular Diet ◽

H Pylori ◽

And Oxidative Stress

Helicobacter pyloriexhibits a high level of intraspecies genetic diversity. In this study, we investigated whether the diversification ofH. pyloriis influenced by the composition of the diet. Specifically, we investigated the effect of a high-salt diet (a known risk factor for gastric adenocarcinoma) onH. pyloridiversification within a host. We analyzedH. pyloristrains isolated from Mongolian gerbils fed either a high-salt diet or a regular diet for 4 months by proteomic and whole-genome sequencing methods. Compared to the input strain and output strains from animals fed a regular diet, the output strains from animals fed a high-salt diet produced higher levels of proteins involved in iron acquisition and oxidative-stress resistance. Several of these changes were attributable to a nonsynonymous mutation infur(fur-R88H). Further experiments indicated that this mutation conferred increased resistance to high-salt conditions and oxidative stress. We propose a model in which a high-salt diet leads to high levels of gastric inflammation and associated oxidative stress inH. pylori-infected animals and that these conditions, along with the high intraluminal concentrations of sodium chloride, lead to selection ofH. pyloristrains that are most fit for growth in this environment.

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Involvement of NLRP3 inflammasome in the impacts of sodium and potassium on insulin resistance in normotensive Asians

British Journal Of Nutrition ◽

10.1017/s0007114517002926 ◽

2018 ◽

Vol 119 (2) ◽

pp. 228-237 ◽

Cited By ~ 11

Author(s):

Zhaofei Wan ◽

Wen Wen ◽

Keyu Ren ◽

Dong Zhou ◽

Junhui Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Nlrp3 Inflammasome ◽

Fasting Blood Glucose ◽

High Salt ◽

Inflammasome Activation ◽

High Salt Diet ◽

Salt Loading ◽

Salt Diet ◽

Active Effects

AbstractSalt, promoting oxidative stress, contributes to insulin resistance, whereas K, inhibiting oxidative stress, improves insulin sensitivity. Oxidative stress activation of NLRP3 inflammasome is a central player in the induction of insulin resistance. Therefore, we hypothesised that NLRP3 inflammasome may mediate the effects of salt and K on insulin resistance. In all, fifty normotensive subjects were recruited from a rural community of Northern China. The protocol included a low-salt diet for 7 d, then a high-salt diet for 7 d and a high-salt diet with K supplementation for another 7 d. In addition, THP-1 cells were cultured in different levels of Na with and without K. The results showed that salt loading elevated fasting blood glucose, insulin and C-peptide levels, as well as insulin resistance, whereas K supplementation reversed them. Meanwhile, additional K reversed the active effects of high salt on NLRP3 inflammasome in both the subjects and THP-1 cells, and the change of insulin resistance index notably related with the alteration of plasma IL-1β, the index of NLRP3 inflammasome activation, during intervention in the subjects. Additional K ameliorated oxidative stress induced by high salt in both the subjects and cultured THP-1 cells, and the change of oxidative stress related with the alteration of plasma IL-1β during intervention in the subjects. In vitro, antioxidant N-acetyl-l-cysteine significantly prevented the active effects of high Na or oxidant Rosup on NLRP3 inflammasome, so did K. Our study indicates that oxidative stress modulation of NLRP3 inflammasome may be involved in the impacts of Na and K on insulin resistance.

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Reproductive parameters and oxidative stress status of male rats fed with low and high salt diet

Journal of Human Reproductive Sciences ◽

10.4103/0974-1208.126308 ◽

2013 ◽

Vol 6 (4) ◽

pp. 267 ◽

Cited By ~ 11

Author(s):

BolanleO Iranloye ◽

AyodeleO Morakinyo ◽

GabrielO Oludare ◽

LucyC Ekeh ◽

NaomiA Esume

Keyword(s):

Oxidative Stress ◽

High Salt ◽

Male Rats ◽

Reproductive Parameters ◽

High Salt Diet ◽

Salt Diet ◽

Oxidative Stress Status ◽

And Oxidative Stress

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Effect of High-Salt Diet on Vascular Relaxation and Oxidative Stress in Mesenteric Resistance Arteries

Journal of Vascular Research ◽

10.1159/000102955 ◽

2007 ◽

Vol 44 (5) ◽

pp. 382-390 ◽

Cited By ~ 77

Author(s):

Jiaxuan Zhu ◽

Tianjian Huang ◽

Julian H. Lombard

Keyword(s):

Oxidative Stress ◽

High Salt ◽

Vascular Relaxation ◽

Resistance Arteries ◽

High Salt Diet ◽

Salt Diet ◽

And Oxidative Stress

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Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells

AJP Renal Physiology ◽

10.1152/ajprenal.00199.2002 ◽

2002 ◽

Vol 283 (5) ◽

pp. F1132-F1141 ◽

Cited By ~ 69

Author(s):

Violeta Alvarez ◽

Yasmir Quiroz ◽

Mayerly Nava ◽

Héctor Pons ◽

Bernardo Rodríguez-Iturbe

Keyword(s):

Interstitial Nephritis ◽

Renal Damage ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Malondialdehyde Content ◽

Induced Hypertension ◽

Salt Sensitive Hypertension ◽

And Control ◽

And Oxidative Stress

Recent evidence suggests that salt-sensitive hypertension develops as a consequence of renal infiltration with immunocompetent cells. We investigated whether proteinuria, which is known to induce interstitial nephritis, causes salt-sensitive hypertension. Female Lewis rats received 2 g of BSA intraperitoneally daily for 2 wk. After protein overload (PO), 6 wk of a high-salt diet induced hypertension [systolic blood pressure (SBP) = 156 ± 11.8 mmHg], whereas rats that remained on a normal-salt diet and control rats (without PO) on a high-salt diet were normotensive. Administration of mycophenolate mofetil (20 mg · kg−1 · day−1) during PO resulted in prevention of proteinuria-related interstitial nephritis, reduction of renal angiotensin II-positive cells and oxidative stress (superoxide-positive cells and renal malondialdehyde content), and resistance to the hypertensive effect of the high-salt diet (SBP = 129 ± 12.2 mmHg). The present studies support the participation of renal inflammatory infiltrate in the pathogenesis of salt-sensitive hypertension and provide a direct link between two risk factors of progressive renal damage: proteinuria and hypertension.

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High-salt diet enhances hippocampal oxidative stress and cognitive impairment in mice

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2014.04.010 ◽

2014 ◽

Vol 114 ◽

pp. 10-15 ◽

Cited By ~ 24

Author(s):

Yun-Zi Liu ◽

Ji-Kuai Chen ◽

Zhang-Peng Li ◽

Ting Zhao ◽

Min Ni ◽

...

Keyword(s):

Oxidative Stress ◽

Cognitive Impairment ◽

High Salt ◽

High Salt Diet ◽

Salt Diet

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Abstract 370: Upregulation of Renal D5 Dopamine Receptor Ameliorates Hypertension in D3 Deficient Mice

Hypertension ◽

10.1161/hyp.60.suppl_1.a370 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Xiaoyan Wang ◽

Crisanto S Escano ◽

Laureano Asico ◽

John E Jones ◽

Alan Barte ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Nadph Oxidase ◽

Protein Expression ◽

Dopamine Receptors ◽

Dopamine Receptor ◽

High Salt ◽

High Salt Diet ◽

Salt Diet ◽

Deficient Mice

D 3 dopamine receptor (D 3 R) deficient mice have renin-dependent hypertension but the hypertension is mild and is not associated with oxidative stress. In order to determine if any compensatory mechanism in the kidney is involved in the regulation of blood pressure with disruption of D 3 R, we measured the renal protein expression of dopamine receptors in D 3 R homozygous (D 3 -/-) and heterozygous (D 3 +/-) knockout mice and their wild type (D 3 +/+) littermates. D 5 dopamine receptor (D 5 R) (169±23%, reported as % of D 3 +/+, n=5/group) expression was increased but D 4 dopamine receptors protein expression (59±8%) was decreased, while no significant changes were found with D 1 and D 2 dopamine receptors. Immunocytochemistry showed a stronger renal staining of D 5 R but without a change in renal tubule cell distribution in D 3 -/- relative to D 3 +/+ mice. D 5 R abundance was also increased in D 3 +/- (205±30%, n=5/group) relative to D 3 +/+ mice, while D 1 R abundance was similar between D 3 +/- and D 3 +/+ mice. The increase in D 5 R expression was abolished while blood pressure was increased further in D 3 -/- mice fed a high salt diet. Treatment of the D 1 -like (including D 1 and D 5 receptors) antagonist, SCH23390 , increased the blood pressure to a greater extent in anesthetized D 3 -/- mice than in D 3 +/+ mice (n=4/group), suggesting that the upregulation of D 5 R may modulate the hypertension in mice caused by the disruption of D 3 R. Since dopamine inhibits the NADPH oxidase-induced production of reactive oxygen species (ROS) via the D 5 R, we also measured the protein expression of NOXs in the kidney and isoprostane in the urine. No NADPH oxidase subunit was increased in D 3 -/- and D 3 +/- mice relative to D 3 +/+ mice fed a normal or salt high salt diet, and urinary isoprostane excretion was also similar in D 3 -/- and D 3 +/+ mice. Our findings suggest that the upregulation of D 5 R may minimize the hypertension and prevent oxidative stress in D 3 -/- mice.

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