Glutathione metabolic enzyme activities in diabetic platelets as a function of glycemic control

Muruganandam, Arumugam; Drouillard, Christine; Thibert, R.J.; Cheung, Rose; Draisey, T.F.; Mutus, Bülent

doi:10.1016/0049-3848(92)90268-f

Cited by 48 publications

(21 citation statements)

References 33 publications

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“…cGPx plays a key role in the protection of cells from oxidative damage and also regulates the formation of eicosanoids, since their formation depends on the peroxide tone of the cells (47,48). According to the literature, the glutathione peroxidase response to diabetes has been conflicting, but, as previously reported (49,50), cGPx activities were found to be lower in the present study. Lower cGPx activity can lead to a relative accumulation of 12-HpETE, the main hydroperoxide formed from arachidonic acid, and such an increase could activate signal transduction pathways leading to arachidonic acid release (12,27), thus amplifying platelet activation.…”

Section: Discussioncontrasting

confidence: 44%

Diabetic Patients Without Vascular Complications Display Enhanced Basal Platelet Activation and Decreased Antioxidant Status

et al. 2004

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Vascular complications are the leading causes of morbidity and mortality in diabetic patients. The contribution of platelets to thromboembolic complications is well documented, but their involvement in the initiation of the atherosclerotic process is of rising interest. Thus, the aim of the present study was to evaluate basal arachidonic acid metabolism in relation to the redox status of platelets in both type 1 and type 2 diabetic patients, in the absence of vascular complications, as compared with respective control subjects. For the first time, we show that basal thromboxane B 2 , the stable catabolite of thromboxane A 2 , significantly increased in resting platelets from both type 1 and type 2 diabetic patients (58 and 88%, respectively), whereas platelet malondialdehyde level was only higher in platelets from type 2 diabetic subjects (67%). On the other hand, both vitamin E levels and cytosolic glutathione peroxidase activities were significantly lower in platelets from diabetic patients as compared with respective control subjects. We conclude that platelet hyperactivation was detectable in well-controlled diabetic patients without complications. This abnormality was associated with increased oxidative stress and impaired antioxidant defense in particular in type 2 diabetic patients. These alterations contribute to the increased risk for occurrence of vascular diseases in such patients. Diabetes

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Section: Discussioncontrasting

confidence: 44%

Diabetic Patients Without Vascular Complications Display Enhanced Basal Platelet Activation and Decreased Antioxidant Status

et al. 2004

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“…Platelet suspension was preincubated under gentle stirring with 200 M diamide to lower reduced glutathione (41) and then slow down GPx, and with 200 M acetylsalicylic acid as a cyclooxygenase inhibitor (42), for 5 min at 37 Њ C. Platelets were then incubated with 300 M AA labeled with 37 kBq of [5,6,8,9,11,12,14, H]AA (7.77 TBq/mmol) for 5 min in the presence of oxygen. Platelet suspension was then acidified to pH 3 with 3 M HCl and treated three times with 3 vol of diethyl ether to extract AA derivatives.…”

Section: Preparation Of 12-hpetementioning

confidence: 99%

Covalent binding of hydroxy-alkenals 4-HDDE, 4-HHE, and 4-HNE to ethanolamine phospholipid subclasses

Bacot

Bernoud-Hubac

Baddas

et al. 2003

Journal of Lipid Research

102

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Lipid oxidation is implicated in a wide range of pathophysiogical disorders, and leads to reactive compounds such as fatty aldehydes, of which the most well known is 4-hydroxy-2 E-nonenal (4-HNE) issued from 15-hydroperoxyeicosatetraenoic acid (15-HpETE), an arachidonic acid (AA) product. In addition to 15-HpETE, 12(S)-HpETE is synthesized by 12-lipoxygenation of platelet AA. We first show that 12-HpETE can be degraded in vitro into 4-hydroxydodeca-(2 E ,6 Z )-dienal (4-HDDE), a specific aldehyde homologous to 4-HNE. Moreover, 4-HDDE can be detected in human plasma. Second, we compare the ability of 4-HNE, 4-HDDE, and 4-hydroxy-2 E -hexenal (4-HHE) from n-3 fatty acids to covalently modify different ethanolamine phospholipids (PEs) chosen for their biological relevance, namely AA-(20: 4n-6) or docosahexaenoic acid-(22:6n-3) containing diacyl-glycerophosphoethanolamine (diacyl-GPE) and alkenylacyl-glycerophosphoethanolamine (alkenylacyl-GPE) molecular species. The most hydrophobic aldehyde used, 4-HDDE, generates more adducts with the PE subclasses than does 4-HNE, which itself appears more reactive than 4-HHE. Moreover, the aldehydes show higher reactivity toward alkenylacyl-GPE compared with diacyl-GPE, because the docosahexaenoyl-containing species are more reactive than those containing arachidonoyl. We conclude that the different PE species are differently targeted by fatty aldehydes: the higher their hydrophobicity, the higher the amount of adducts made. In addition to their antioxidant potential, alkenylacyl-GPEs may efficiently scavenge fatty aldehydes. Supplementary key words 4-hydroxydodeca-(2 E ,6 Z )-dienal • 4-hydroxy-2 E -hexenal • 4-hydroxy-2 E -nonenal

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“…The ion at m/z 227 is common to the three adducts and presumably derives from the [M-114] I2 ion by molecular rearrangement, whereas m/z 113 corresponds to the [CF 3 -COO] 2 ion. Typical SIM profiles of standard ethanolamine adducts derivatized by TFAI are shown in Fig.…”

Section: I2mentioning

confidence: 99%

“…Minor ions resulting from the loss of fluorhydric acid [M-20] I were found at m/z 541, 583, and 623, respectively. A rearrangement of the molecular anion radicals with loss of CF 3 …”

Section: Characterization Of Chemically Synthesized Pe-alkenal Michaementioning

confidence: 99%

“…Those hydroperoxides are normally reduced to their corresponding alcohols by glutathione peroxidases (1). However, glutathione peroxidase activities have been shown to be decreased in aging (2) and diabetes (3,4), resulting in a transient accumulation of lipid hydroperoxides that favors their degradation into several compounds, including hydroxy-alkenals. The most well known of these are 4-hydroxy-2(E)-nonenal (4-HNE) (5) and 4-hydroxy-2(E)-hexenal (4-HHE) (6), which derive from n-6 and n-3 fatty acid peroxidation, respectively.…”

mentioning

confidence: 99%

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Evidence for in situ ethanolamine phospholipid adducts with hydroxy-alkenals

Bacot

Bernoud-Hubac

Chantegrel

et al. 2007

Journal of Lipid Research

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Hydroxy-alkenals, such as 4-hydroxy-2(E )-nonenal (4-HNE; from n-6 fatty acids), are degradation products of fatty acid hydroperoxides, including those generated by free radical attack of membrane polyunsaturated fatty acyl moieties. The cytotoxic effects of hydroxy-alkenals are well known and are mainly attributable to their interaction with different molecules to form covalent adducts. Indeed, ethanolamine phospholipids (PEs) can be covalently modified in a cellular system by hydroxy-alkenals, such as 4-HNE, 4-hydroxy-2(E)-hexenal (4-HHE; from n-3 fatty acids), and 4-hydroxy-dodecadienal (4-HDDE; from the 12-lipoxygenase product of arachidonic acid), to form mainly Michael adducts. In this study, we describe the formation of PE Michael adducts in human blood platelets in response to oxidative stress and in retinas of streptozotocin-induced diabetic rats. We have successfully characterized and evaluated, for the first time, PEs coupled with 4-HHE, 4-HNE, and 4-HDDE by gas chromatography-mass spectrometry measurement of their ethanolamine moieties. We also report that aggregation of isolated human blood platelets enriched with PE-4-hydroxy-alkenal Michael adducts was altered. These data suggest that these adducts could be used as specific markers of membrane disorders occurring in pathophysiological states with associated oxidative stress and might affect cell function.-Bacot, S., N. Bernoud-Hubac, B. Chantegrel, C. Deshayes, A. Doutheau, G. Ponsin, M. Lagarde, and M. Guichardant. Evidence for in situ ethanolamine phospholipid adducts with hydroxy-alkenals. J. Lipid Res. 2007. 48: 816-825.

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Glutathione metabolic enzyme activities in diabetic platelets as a function of glycemic control

Cited by 48 publications

References 33 publications

Diabetic Patients Without Vascular Complications Display Enhanced Basal Platelet Activation and Decreased Antioxidant Status

Diabetic Patients Without Vascular Complications Display Enhanced Basal Platelet Activation and Decreased Antioxidant Status

Covalent binding of hydroxy-alkenals 4-HDDE, 4-HHE, and 4-HNE to ethanolamine phospholipid subclasses

Evidence for in situ ethanolamine phospholipid adducts with hydroxy-alkenals

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