Platelet surface glutathione reductase-like activity

Essex, David W.; Li, Mengru; Feinman, Richard D.; Miller, Anna

doi:10.1182/blood-2004-03-1097

Cited by 38 publications

(41 citation statements)

References 20 publications

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“…34 Recently, it has been described that platelets contain a glutathione reductase-like activity on their surface, which participates in regulating the extracellular GSH/GSSG ratio, and is capable of generating the appropriate redox potential for platelet activation. 79 Similar mechanisms have been observed to regulate collagen-dependent platelet adhesion to the ␣ 2␤1 integrin 80 and are proposed to participate in inactivation of the platelet P 2 Y 12 receptor. 81 Independent from this, another oxidative platelet activatory mechanism involves the short intracellular tail of ␤ 3 , which can be tyrosine phosphorylated on extracellular ligand binding.…”

Section: Role Of Ros In Platelet Signalingmentioning

confidence: 87%

Reactive Oxygen Species

Krötz

Sohn

Pohl

2004

ATVB

408

122

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Abstract-Platelets participate not only in thrombus formation but also in the regulation of vessel tone, the development of atherosclerosis, angiogenesis, and in neointima formation after vessel wall injury. It is not surprising, therefore, that the platelet activation cascade (including receptor-mediated tethering to the endothelium, rolling, firm adhesion, aggregation, and thrombus formation) is tightly regulated. In addition to already well-defined platelet regulatory factors, such as nitric oxide (NO), prostacyclin (PGI 2 ), and adenosine, reactive oxygen species (ROS) participate in the regulation of platelet activation. Although exogenously derived ROS are known to affect the regulation of platelet activation, recent data suggest that the platelets themselves generate ROS. Intracellular ROS signaling in activated platelets could be of significant relevance after transient platelet contact with the vessel wall, during the recruitment of additional platelets, and in thrombus formation. This review discusses the potential cellular and enzymatic sources of ROS in platelets, their molecular mechanisms of action in platelet activation, and summarizes in vitro and in vivo evidence for their physiological and potential therapeutic relevance. Key Words: platelets Ⅲ reactive oxygen species Ⅲ NAD(P)H-oxidase Ⅲ aggregation Ⅲ adhesion Ⅲ thrombus formation P latelet interaction with the vessel wall serves numerous physiological and pathophysiological functions. This is reflected by the fact that platelets release growth factors, 1 lipid mediators, 2,3 and cytokines. 4 Consequently, the regulation of platelet activity plays a role not only for thrombus formation and the regulation of vascular tone 5 but also for the vascular pathophysiology of angiogenesis and inflammation. Moreover, platelets participate in the development of atherothrombotic disease by promoting atherosclerotic lesion 6 and neointima formation. 7 Not surprisingly, the activation of platelets is regulated and modulated by numerous factors, blood-borne and cell-derived. Most of these factors are relatively well-characterized. 8 However, in recent time, several publications have suggested that reactive oxygen species (ROS) represent a new modulator of platelet activity. It has been known for some time that ROS exert critical regulatory functions within the vascular wall and it is therefore plausible that platelets represent a relevant target for their action.Within the vessel wall (where endothelial cells, vascular smooth muscle cells, and fibroblasts express a variety of ROS-generating enzymes), there is a constant, low-quantity flux of ROS. It is already established that enhanced ROS release from the vascular wall can indirectly affect platelet activity by scavenging nitric oxide (NO), thereby decreasing the antiplatelet properties of the endothelium. 9 In addition to their exposure to ROS derived from the vascular wall, platelets themselves also can generate ROS, and there is some evidence for a more direct role of ROS in the control of platelet activi...

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Section: Role Of Ros In Platelet Signalingmentioning

confidence: 87%

Reactive Oxygen Species

Krötz

Sohn

Pohl

2004

ATVB

408

122

View full text Add to dashboard Cite

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“…Inhibited NADPH oxidases activities thus reduce the consumption of intracellular NADPH and then increased GSH synthesis because NADPH is a key element of GSH synthesis. Cells use NADPH as an electron donor to reduce the GSSG to GSH through the catalysis of GSH reductase and maintain the high GSH levels in the cells [29]. Platelet NADPH oxidases are major sources of platelet superoxide [30], which have been found to be essential in regulating platelet activation [30], but it may also be a main cause for enhancing platelet oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Zinc Deficiency Increases Platelet Oxidative Stress in Nephrectomized Rats

Chen

Kuo

et al. 2007

Biol Trace Elem Res

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We previously reported that reduced platelet endogenous antioxidant enzymes activities are related to the low plasma zinc level in patients with end-stage renal failure (ESRF). In this study, we attempt to evaluate whether dietary zinc deprivation reduces the activities of endogenous antioxidant and then enhances oxidative stress in the unstimulated platelet of normal and 5/6 nephrectomized (Nx) rats because increased platelet oxidative stress is suggested to involve in the incidence of thrombotic and atherosclerotic diseases. Male Sprague-Dawley rats (n = 48) were fed a zinc-deficient diet and deionized distilled water for 1 week to induce reduction of plasma zinc level. Half of the rats continued on this diet for 4 weeks as zinc-deplete group, and the other half were maintained on the same diet but with zinc-supplemented water (120 mg/L zinc sulfate solution) to correct the reduction of plasma zinc level as zinc-replete group. Half of each group underwent 5/6 Nx, while the other half underwent sham operation. Another 12 normal rats were fed standard rat chow (containing 23.4% protein and 50 ppm zinc) and drank deionized distilled water as normal control rats. In zinc-deplete rats including sham-operated and 5/6 Nx rats exhibited lower endogenous antioxidant enzymes activities such as reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) and higher malondialdehyde (MDA) levels than normal control rats in the unstimulated platelets. However, in zinc-replete rats including sham-operated and 5/6 Nx rats have a normal endogenous antioxidant enzymes activity and normal MDA levels in the unstimulated platelets. We suggest that in uremia, the low plasma zinc level may be a risk factor for thrombotic and atherosclerotic diseases because it reduces the activities of endogenous antioxidant enzymes and increases oxidative stress in the unstimulated platelet.

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“…GP IIb/IIIa'nın membran dış yüzeyinde yer alan uçları disülfit bağlarından zengindir ve redüksiyonla birlikte aktive olur. Gp IIb/IIIa'daki serbest tiyol grupları ekstraselüler GSH / GSSG oranıyla kontrol edilir (23). Dolayısıyla hem intraselü-ler ve ekstraselüler ROT konsantrasyonu ve GSH /GSSG oranı trombosit fonksiyonlarının önemli düzenleyicileridir.…”

Section: Discussionunclassified