Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation.

Ohara, Yoshio; Peterson, Timothy E.; Zheng, Bin; Kuo, J.F.; Harrison, David G.

doi:10.1161/01.atv.14.6.1007

Cited by 126 publications

(72 citation statements)

References 40 publications

(25 reference statements)

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“…PKC-β has significant actions in endothelial and smooth muscle cells of blood vessels [1,28]. PKC may contribute to abnormal vascular reactivity via increased production of superoxide radicals [20], and in endothelial cells it may impair NO production by reducing NO synthase protein levels [29]. In vascular smooth muscle, enhanced PKC-β 2 activity is associated with hypertrophy and hyperplasia [4].…”

Section: Discussionmentioning

confidence: 99%

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Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

et al. 2004

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Aims/hypothesis. The impact of early vitamin E supplementation on vascular function in diabetes remains unresolved. Therefore, we examined the effects of vitamin E on functional and structural parameters and on chemical markers that are disturbed in diabetes in mesenteric and femoral arteries. Methods. Segments of both arteries, taken from control and 8-week-old streptozotocin diabetic Wistar rats that were treated or not with vitamin E, were mounted on wire and pressure myographs, after which endothelium-dependent and -independent vasodilation was assessed. Passive mechanical wall properties and the localisation and levels of protein kinase C (PKC)-β 2 and AGE were evaluated in these vessels. Results. Vitamin E supplementation was associated with improved endothelium-dependent and -independent vasodilatation in mesenteric arteries from diabetic rats. Impaired endothelium-dependent vasodilatation in diabetic mesenteric vessels was associated with PKC-β 2 up-regulation and this was prevented by vitamin E supplementation. Increased AGE accumulation and plasma isoprostane levels in diabetic rats were not changed by vitamin E. In the femoral artery, vitamin E supplementation had no effect on endothelium-dependent or -independent vasodilatation, but did prevent the wall stiffening associated with diabetes. Conclusions/interpretation. Early vitamin E supplementation has a beneficial effect on diabetes-induced endothelial dysfunction in resistance arteries. This benefit may arise from a direct effect on smooth muscle function, as a result of inhibition of the PKC-β 2 isoform by vitamin E. Abbreviations: ACh, acetylcholine · EDHF, endothelium-derived hyperpolarising factor · GHb, glycohaemoglobin · h, wall thickness · ID, internal diameter · L, length · l-NAME, N ω -nitro-L-arginine methyl ester · NO, nitric oxide · OD, outside diameter · P, intraluminal pressure · PKC, protein kinase C · PSS, physiological saline solution · SNP, sodium nitroprusside · STZ, streptozotocin · VitE, vitamin E supplementation · V max , maximal relaxation

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Section: Discussionmentioning

confidence: 99%

“…A modification of the ABC immunoglobulin enzyme bridge technique [20] was used on formalin-fixed paraffin sections of vessels. Endogenous peroxidase activity was eliminated by incubating sections in 0.3% hydrogen peroxide for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

et al. 2004

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“…Advanced glycation end products could induce radical formation directly as well as indirectly by activating their cellular receptors (RAGE) [30,31,32]. In addition, hyperglycaemia leads to activation of protein kinase C [33,34], which has also been shown to result in the induction of oxygen radical stress [35]. Activation of the polyol pathway by hyperglycaemia and glucoseauto oxidation are able to induce oxygen radical stress [36,37].…”

Section: Discussionmentioning

confidence: 99%

Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate

et al. 2002

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Aims/hypothesis. Patients with diabetes are characterised by endothelial dysfunction and cardiovascular mortality. In particular endothelium-derived nitric oxide has emerged as a first line mechanism against atherosclerosis. Hyperglycaemia causes oxygen radical stress but has also been associated with endothelial nitric oxide synthase uncoupling, both lead to decreased nitric oxide-availability. We recently showed that folate reverses eNOS uncoupling in vitro. Therefore we hypothesise that folate improves endothelial function in Type II (non-insulin-dependent) diabetes mellitus in vivo. Methods. Using forearm plethysmography, we evaluated the effect of local, intra-arterial administration of 5-methyltetrahydrofolate (5-MTHF, the active form of folic acid, 1 µg/100 ml FAV/min) on forearm blood flow in 23 patients with Type II diabetes and 21 control subjects, matched for age, sex, blood pressure, body mass index, weight and smoking habits. Serotonin as a stimulator of nitric oxide-dependent vasodilation and sodium nitroprusside as a stimulator of endothelium-independent vasodilation were infused. Results. Serotonin-induced vasodilation was blunted (53±30 vs 102±66 M/C%, p<0.005) and nitroprussideinduced vasodilation was mildly reduced (275±146 vs 391±203 M/C%, p<0.05) in patients with Type II diabetes compared to control subjects. 5-MTHF improved nitric oxide-mediated vasodilation (from 53±30 to 88±59 M/C%, p<0.05) in patients with Type II diabetes mellitus. As expected, 5-MTHF had no effect on forearm blood flow in control subjects. Conclusion/interpretation. These data imply that folate can be used to improve nitric oxide status and to restore endothelial dysfunction in patients with Type II diabetes. Our results provide a strong rationale for the initiation of studies that investigate whether supplementation with folic acid prevents future cardiovascular events in this patient group. [Diabetologia (2002[Diabetologia ( ) 45:1004[Diabetologia ( -1010

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“…11,35 In the case of vascular smooth muscle cells, LPC generates O 2 .Ϫ through PKC activation, and the activity might be mediated by Ca 2ϩ influx. 36 However, LPC-mediated O 2 .Ϫ generation in human neutrophils occurs through PI3 kinase activation but not through PKC. 37 In ventricular myocytes, LPC modulates the Na ϩ current by PKC-dependent and tyrosine kinasedependent phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Decreases in ANP Secretion by Lysophosphatidylcholine Through Protein Kinase C

et al. 2003

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Abstract-Lysophosphatidylcholine (LPC) is an endogenous phospholipid released from the cell membrane during ischemia, and it has potent, local effects on cardiac tissues. LPC has been implicated in arrhythmogenesis during ischemia by increasing intracellular Ca 2ϩ . However, it is not known whether LPC influences atrial release of atrial natriuretic peptide (ANP). The aim of this study was to investigate the effect of LPC on ANP secretion from isolated, perfused, beating rat atria. LPC (10 and 30 mol/L) caused decreases in ANP secretion in a dose-dependent manner, with slight increases in intra-atrial pressure and extracellular fluid (ECF) translocation. Therefore, the ANP secretion in terms of ECF translocation was markedly decreased by LPC. The order of the suppressive effect of ANP release was stearoyl-LPCϾLPCϾmyristoyl-LPCϭlauroyl-LPC. Staurosporine and wortmannin significantly attenuated suppression of the ANP release and an increase in intra-atrial pressure by LPC. High extracellular Mg 2ϩ also attenuated the LPC-induced suppression of ANP release. However, other protein kinase C inhibitors such as chelerythrine, GF 109203X, and tamoxifen citrate did not affect LPC-induced suppression of ANP release. In single atrial myocytes, LPC caused increases in intracellular Ca 2ϩ in a dose-dependent manner. The order of an increase in intracellular Ca 2ϩ by LPC was stearoyl-LPCϾLPCϾmyristoyl-LPCϭlauroyl-LPC. An increase in intracellular Ca 2ϩ by LPC was attenuated by staurosporine. These results suggest that LPC-induced suppression of ANP release through protein kinase C/Ca 2ϩ and phosphoinositol-3-kinase might in part play an important role in the development of hypertension.

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Lysophosphatidylcholine increases vascular superoxide anion production via protein kinase C activation.

Cited by 126 publications

References 40 publications

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate

Decreases in ANP Secretion by Lysophosphatidylcholine Through Protein Kinase C

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