Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Qadri, S. M. Hussain; Shao‐Horn, Yang; Cayabyab, Francisco S.; Liu, Lixin

doi:10.1186/preaccept-2049863413138121

Cited by 5 publications

(6 citation statements)

References 57 publications

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“…Despite the large amount of evidence for HG or MGO-induced oxidative stress, the mechanisms whereby ROS formation is induced, are not fully understood. Recently it was reported that MGO-stimulated ROS production activates the endothelial plasma membrane transport protein, Na + /H + exchanger (NHE1) [ 30 ]. Moreover HG-induced vascular deficits are related to hyperactivity of NHE1 [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum

Boydens

Pauwels

Daele

et al. 2016

Cardiovasc Diabetol

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BackgroundHyperglycemia and increased levels of methylglyoxal (MGO) can trigger the development of vascular complications in diabetes. Resveratrol and quercetin are red wine polyphenols with known beneficial cardiovascular properties, including an antioxidant capacity. This study evaluated whether resveratrol and/or quercetin could prevent in vitro-induced diabetic changes in neurogenic and vascular relaxant responses of mouse arteries and corpora cavernosa.MethodsIsometric tension of isolated aorta, mesenteric arteries and corpora cavernosa was measured using organ bath systems. Diabetic conditions were mimicked in vitro by co-incubating the tissues for 2 h with high glucose (HG, 30 mM) and MGO (120 µM).ResultsThe presence of HG and MGO significantly blunted acetylcholine (Ach)-induced relaxations in corpora cavernosa and mesenteric arteries but not in aorta. Electrical field stimulated (EFS) responses of corpora cavernosa were also significantly inhibited by these diabetic conditions. In corpora cavernosa 2 h co-incubation with resveratrol (30 µM) or quercetin (30 µM) significantly attenuated HG and MGO-induced deficits in Ach- and EFS-responses.ConclusionsOur study demonstrates that in mouse arteries, HG and MGO rather affect endothelium derived hyperpolarizing factor-mediated than nitric oxide (NO)-mediated relaxations. In corpora cavernosa HG and MGO interfere with NO release. Resveratrol and quercetin protect mouse corpora cavernosa from diabetic-induced damage to NO-mediated relaxant responses. This might rely on their antioxidant capacity.

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Section: Discussionmentioning

confidence: 99%

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum

Boydens

Pauwels

Daele

et al. 2016

Cardiovasc Diabetol

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“…The present study uncovers a novel functional role of the DJ‐1 protein, that is, the regulation of NHE1 activity and ROS production in CD4 + T cells. Our findings are the first to reveal enhanced Na + /H + exchanger 1 activity in DJ‐1 deficient CD4 + T cells, which is apparent without any treatment with cytokines (IL‐2, IFN‐γ), growth factors (EGF, angiotensin II) and hormones (glucocorticoids) (Chang et al, ; Voelkl et al, ; Chatterjee et al, ; Qadri et al, ). The effect of DJ‐1 on NHE1 activity is at least in part due to an impact of DJ‐1 on NHE1 expression, as it is paralleled by higher abundance of NHE1 mRNA levels and NHE1 protein abundance.…”

Section: Discussionmentioning

confidence: 56%

“…ROS production is paralleled by and requires H + extrusion by the Na + /H + exchanger 1 (NHE1) (Rotte et al, , ; Yang et al, ; Alvarez and Villa‐Abrille, ; Prasad et al, ; Qadri et al, ; Park et al, ), which participates in the regulation of intracellular pH (pH i ) (De Vito, ). Further, functions of NHE1 include regulation of cell volume, proliferation, and motility (Putney and Barber, ; De Vito, ).…”

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confidence: 99%

DJ‐1/Park7 Sensitive Na⁺/H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells

Zhou

Shi

Chen

et al. 2017

Journal Cellular Physiology

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DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na /H exchanger 1 (NHE1). ROS formation in CD4 T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-1 is expressed in CD4 T cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ-1 and NHE1 transcript, and protein levels were quantified by qRT-PCR and Western blotting, respectively, intracellular pH (pH ) utilizing bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed in CD4 T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4 T cells from DJ-1 deficient mice than in CD4 T cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1 deficient CD4 T cells, and blunted the difference between DJ-1 and DJ-1 CD4 T cells, an observation pointing to a role of ROS in the up-regulation of NHE1 in DJ-1 CD4 T cells. In conclusion, DJ-1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4 T cells. J. Cell. Physiol. 232: 3050-3059, 2017. © 2016 Wiley Periodicals, Inc.

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“…Moreover, it has been shown that plasma concentrations of MG above 600 nM discriminate between diabetic individuals with pain and those without pain (Bierhaus et al, ). Concentrations in the same range as those used in our report (higher than 100 μM MG) were used in recent in vitro studies investigating the effects of MG on ion channels and transporters (Ohkawara et al, ; Quadri et al, ; Yang et al, ) and in experiments carried out on isolated rat thoracic aorta (Mukohda et al, ). In the bowel, the relevant concentrations could be even higher than the ones used in this work (Zhang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Glycolytic metabolite methylglyoxal inhibits cold and menthol activation of the transient receptor potential melastatin type 8 channel

Ciobanu

Şelescu

Gasler

et al. 2015

J of Neuroscience Research

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Methylglyoxal (MG) is a reactive dicarbonyl compound involved in protein modifications linked to diabetes mellitus. The plasma level of MG is elevated in diabetic patients, particularly those with painful diabetic neuropathy. Diabetic neuropathy is often associated with spontaneous pain and altered thermal perception. This study assesses effects of MG on TRPM8, an ion channel involved in innocuous cold sensing and cold allodynia and also in cold-mediated analgesia. Acute treatment with MG inhibited the activation of recombinant rat and human transient receptor potential melastatin type 8 (TRPM8) by cold and chemical agonists. A similar effect was observed when native TRPM8 was investigated in cultured rat dorsal root ganglion (DRG) neurons. DRG neurons treated with MG for 16-24 hr displayed a significant reduction in the fraction of cold- and menthol-sensitive neurons, most likely expressing TRPM8. The fraction of allyl isothiocyanate-sensitive neurons was also reduced, and the coexpression among different neuronal populations was affected. The same prolonged exposure to MG significantly reduced the expression of TRPM8 at the mRNA level. Overall, our data provide evidence for decreased activity and expression level of TRPM8 in the presence of MG, which may be linked to some of the alterations in pain and temperature sensing reported by diabetic patients. © 2015 Wiley Periodicals, Inc.

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Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Cited by 5 publications

References 57 publications

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum

DJ‐1/Park7 Sensitive Na⁺/H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells

Glycolytic metabolite methylglyoxal inhibits cold and menthol activation of the transient receptor potential melastatin type 8 channel

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Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

Cited by 5 publications

References 57 publications

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum

Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum

DJ‐1/Park7 Sensitive Na+/H+ Exchanger 1 (NHE1) in CD4+ T Cells

Glycolytic metabolite methylglyoxal inhibits cold and menthol activation of the transient receptor potential melastatin type 8 channel

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DJ‐1/Park7 Sensitive Na⁺/H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells