Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells

Yamawaki, Hideyuki; Saito, Keigo; Okada, Muneyoshi; Hara, Yukio

doi:10.1152/ajpcell.00252.2008

Cited by 87 publications

(67 citation statements)

References 40 publications

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“…Western blotting was performed as described previously (15,17,20,21). Protein lysates were obtained by homogenizing the arterial preparations in Triton-based lysis buffer (1% Triton X-100, 20 mM Tris, pH 7.4, 150 mM NaCl, 1 mM β-glycerol phosphate, 1 mM NA 3 VO 4 , 1 μg/mL leupeptin, and 0.1% protease inhibitor mixture; Nacalai Tesque, Kyoto).…”

Section: Western Blottingmentioning

confidence: 99%

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

et al. 2012

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Abstract. Methylglyoxal (MGO) is a metabolite of glucose and perhaps mediates diabetesrelated macrovascular complications including hypertension. In the present study, we examined if MGO accumulation affects vascular reactivity of isolated mesenteric artery from spontaneously hypertensive rats (SHR). Five-week-old SHR were treated with an MGO scavenger, aminoguanidine (AG), for 5 weeks. AG partially normalized increased blood pressure in SHR. In mesenteric artery from SHR treated with AG, increased accumulation of MGO-derived advanced glycation end-products was reversed. In mesenteric artery from SHR, AG normalized impaired acetylcholine (ACh)-induced relaxation and increased angiotensin (Ang) II-induced contraction. Reactive oxygen species (ROS) production increased in SHR mesenteric artery, and acute treatment with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) inhibitor augmented AChinduced relaxation. Protein expression of NOX1 and Ang II type 2 receptor (AT2R) increased in SHR mesenteric artery, which was normalized by AG. Acute treatment with an AT2R blocker but not a NOX inhibitor normalized the increased Ang II-induced contraction in SHR mesenteric artery. The present results demonstrate that MGO accumulation in mesenteric artery may mediate development of hypertension in SHR at least in part via increased ROS-mediated impairment of endothelium-dependent relaxation and AT2R-mediated increased Ang II contraction.

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Section: Western Blottingmentioning

confidence: 99%

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

et al. 2012

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“…Human umbilical vein endothelial cells (HUVECs) were obtained from Kurabo (Osaka) and cultured in Medium 200 supplemented with low serum growth supplement (Cascade Biologics, Portland, OR, USA) as described previously (10,11). Cells at passages from 4 to 7 were used.…”

Section: Cell Culturementioning

confidence: 99%

“…Immunofluorescence staining was done as described previously (10,11). Cells fixed with 4% paraformaldehyde (pH 7.4) for 10 min at 4°C were permeabilized with 0.1% Triton X-100 for 15 min at room temperature.…”

Section: Immunofluorescence Stainingmentioning

confidence: 99%

CV-159, a Unique Dihydropyridine Derivative, Prevents TNF-Induced Inflammatory Responses in Human Umbilical Vein Endothelial Cells

et al. 2010

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Abstract. CV-159, a 1,4-dihydropyridine derivative, has Ca 2+ antagonistic and anti-calmodulin actions. An early feature of atherosclerosis is vascular endothelial inflammatory change. We examined whether CV-159 has protective effects against endothelial inflammatory responses. After pretreatment of human umbilical vein endothelial cells (ECs) with CV-159 (10 μ M, 30 min), TNF-α (10 ng/ml) was applied for 20 min or 24 h. Expressions of inflammatory markers and activation of inflammatory signal molecules were examined by Western blotting. Reactive oxygen species (ROS) generation was examined by using 2′,7′-dichlorodihydrofluorescein diacetate. CV-159 inhibited TNF (24 h)-induced expression of e-selectin but not vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. CV-159 inhibited TNF (20 min)-induced phosphorylation of JNK, p38, and NF-κ B p65 (Ser536). A JNK inhibitor, SP600125, and a p38 inhibitor, SB203580, inhibited TNF-induced e-selectin expression. An antioxidant drug, N -acetyl-L -cysteine (NAC), inhibited TNF-induced e-selectin expression. NAC inhibited TNF-induced phosphorylation of JNK and p38 but not NF-κ B. CV-159 inhibited TNF-induced ROS generation. Our results indicate that in ECs CV-159 specifically inhibits TNF-induced e-selectin expression through inhibition of JNK, p38, and NF-κ B phosphorylation. It is suggested that CV-159 prevents activation of JNK and p38 through inhibition of ROS, while it prevents activation of NF-κ B via a ROS-independent manner.

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“…Western blotting was performed as described previously (17,18). Protein lysates were obtained by homogenizing SMCs with Triton-based lysis buffer (1% Triton X-100, 20 mM Tris, pH 7.4, 150 mM NaCl, 1 mM EDTA, 1 mM EGTA, 2.5 mM sodium pyrophosphate, 1 mM β -glycerol phosphate, 1 mM NA 3 VO 4 , 1 μ g/ml leupeptin, and 0.1% protease inhibitor cocktail; Nacalai Tesque, Kyoto).…”

Section: Western Blottingmentioning

confidence: 99%

Mechanisms Underlying the Anti-inflammatory Effects of the Ca2+/Calmodulin Antagonist CV-159 in Cultured Vascular Smooth Muscle Cells

et al. 2010

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Abstract. CV-159 is a unique dihydropyridine Ca2+ antagonist with an anti-calmodulin (CaM) action. A pathogenic feature of atherosclerosis is vascular inflammatory change. In the present study, we examined whether CV-159 exerts protective effects on smooth muscle inflammatory responses. After pretreatment of rat mesenteric arterial smooth muscle cells (SMCs) with CV-159 (0.1 -10 μ M, 30 min), TNF-α (10 ng/ml) was applied for 20 min or 24 h. CV-159 inhibited TNF (24 h)-induced vascular cell adhesion molecule (VCAM)-1 as determined by Western blotting. CV-159 inhibited TNF (20 min)-induced phosphorylation of Akt (Ser473) and NF-κ B p65 (Ser536). An Akt inhibitor, LY294002, and an NF-κ B inhibitor, pyrrolidine dithiocarbamate, inhibited TNF-induced VCAM-1. An antioxidant drug, N -acetyl-L -cysteine (NAC) inhibited TNFinduced VCAM-1. NAC also inhibited TNF-induced phosphorylation of Akt and NF-κ B. Furthermore, CV-159 inhibited TNF-induced reactive oxygen species (ROS) production as determined fluorometrically using dichlorodihydrofluorescein diacetate. A CaM inhibitor, W-7, and a calcium/ CaM-dependent protein kinase type II inhibitor, KN93, inhibited TNF-induced VCAM-1. W-7 and KN93 inhibited TNF-induced phosphorylation of Akt but not NF-κ B. The present results indicate that in vascular SMCs, CV-159 inhibits TNF-induced VCAM-1 through inhibition of NF-κ B and Akt phosphorylation. CV-159 prevents NF-κ B phosphorylation by inhibiting ROS, while it prevents Akt phosphorylation by inhibiting both ROS and CaM.

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Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells

Cited by 87 publications

References 40 publications

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

Methylglyoxal Accumulation in Arterial Walls Causes Vascular Contractile Dysfunction in Spontaneously Hypertensive Rats

CV-159, a Unique Dihydropyridine Derivative, Prevents TNF-Induced Inflammatory Responses in Human Umbilical Vein Endothelial Cells

Mechanisms Underlying the Anti-inflammatory Effects of the Ca2+/Calmodulin Antagonist CV-159 in Cultured Vascular Smooth Muscle Cells

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