Oxidative stress and atherosclerosis

Schulze, P. Christian; Lee, Richard T.

doi:10.1007/s11883-005-0013-5

Cited by 83 publications

(50 citation statements)

References 52 publications

(44 reference statements)

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“…In this study, we also showed that palmitate induced apoptosis through ROS generation in HUVECs. Despite recent studies concerning the role of ROS as a signaling molecule (Avshalumov et al 2007), the imbalance between detoxifying antioxidant system and ROS generation leads to divergent pathological disorders (Stocker & Keaney 2004, Schulze & Lee 2005, Takimoto & Kass 2007. Accumulating evidence also indicates that ROS mediates endothelial cell apoptosis to many different stresses such as bacterial toxin, cytokine, and neuronal hormone (Deshpande et al 2000, Suematsu et al 2002, Sylte et al 2004, Kuckleburg et al 2008.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase

Kim¹,

Song²,

Kim³

et al. 2010

Journal of Endocrinology

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The present study examined whether adiponectin can inhibit palmitate-induced apoptosis, and also the associated mechanisms and signal transduction pathways in human umbilical vein endothelial cells. Cells treated with 500 mM palmitate for 48 h increased reactive oxygen species (ROS) generation and induced apoptosis. Treatment with antioxidant N-acetyl-L-cysteine (1 mM) and globular adiponectin (5 mg/ml) inhibited palmitate-induced ROS generation and apoptosis. The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside (AICAR; 1 mM), and cAMP activators forskolin (10 mM) and cholera toxin (200 ng/ml) also displayed the same effects. The inhibitory effects of adiponectin on ROS generation and apoptosis were reversed by the AMPK inhibitor compound C (40 mM), cAMP inhibitor SQ22536 (50 mM), and protein kinase A (PKA) inhibitor H-89 (10 mM). The inhibitory effect of forskolin on palmitateinduced apoptosis was reversed by compound C, whereas the inhibitory effect of AICAR was not reversed by SQ22536 and H-89. AICAR and forskolin could not inhibit palmitate-induced apoptosis in cells treated with dominantnegative AMPK. Forskolin increased phosphorylated AMPK at both Thr-172 and Ser-485/491. These results suggest that adiponectin inhibits palmitate-induced apoptosis by suppression of ROS generation via both the cAMP/PKA and AMPK pathways. Interaction between cAMP/PKA and AMPK pathways may be involved.

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Section: Discussionmentioning

confidence: 99%

Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase

Kim¹,

Song²,

Kim³

et al. 2010

Journal of Endocrinology

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“…Hence, there are two possible explanations for the association between serum GGT and cardiovascular risk: either GGT derives in part from atheromatous plaques, which would be more common and diffuse in patients with adverse cardiovascular risk profiles, or GGT is associated with the risk factors even before the plaques are fully developed. In this context, oxidative stress might be a unifying mediator, because it is closely related to numerous pathological conditions, including atherosclerosis 6,18) . It is also a fundamental component of various pathways implicated in inflammation 19) .…”

Section: Pathogenetic Rolementioning

confidence: 99%

Gamma-glutamyltransferase to Determine Cardiovascular Risk: Shifting the Paradigm Forward

Turgut

Tandoğan

2011

JAT

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Gamma-glutamyltransferase (GGT), regarded as a marker of excessive alcohol consumption or liver disturbances, is an enzyme catalyzing the first step in the extracellular degradation of the antioxidant glutathione (GSH) and may take part in atherogenesis. The marked relationship between GGT and the atherosclerotic process has shifted attention to the issue of whether its serum levels can aid in the detection of individuals at high risk for incident cardiovascular events. It is likely that the process entails the oxidation of low-density lipoprotein through GSH/GGT-dependent iron reduction within the plaque. In this context, oxidative stress is a probable mediator. Recent insights into the pathophysiological background of GGT in the precipitation and progression of atherosclerosis appear to be supported by relevant epidemiological observations as a cardiovascular risk predictor. Further understanding is, nevertheless, warranted to ameliorate the prognostic stratification of patients through GGT.

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“…A growing body of evidence implicates oxidative stress as an important pathogenic element in a variety of diseases, including atherosclerosis and diabetes (34,36). Previous investigations suggest that supplements of LA reduce oxidative stress in both diabetic patients and animal models (9,24) and that it is particularly suitable for prevention and/or treatment of diabetic complications (28).…”

Section: R-␣-lipoic Acid (68-thioctic Acid) (La) Is a Crucial Cofactormentioning

confidence: 99%

Endogenous Production of Lipoic Acid Is Essential for Mouse Development

Maeda

2005

Molecular and Cellular Biology

115

102

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␣-Lipoic acid (LA) is a cofactor for mitochondrial ␣-ketoacid dehydrogenase complexes and is one of the most potent, natural antioxidants. Reduction of oxidative stress by LA supplementation has been demonstrated in patients with diabetic neuropathy and in animal models. To determine how normal development or pathological conditions are affected by genetic alterations in the ability of mammalian cells to synthesize LA and whether dietary LA can circumvent its endogenous absence, we have generated mice deficient in lipoic acid synthase (Lias). Mice heterozygous for disruption of the Lias gene develop normally, and their plasma levels of thiobarbituric acid-reactive substances do not differ from those of wild-type mice. However, the heterozygotes have significantly reduced erythrocyte glutathione levels, indicating that their endogenous antioxidant capacity is lower than those of wild-type mice. Homozygous embryos lacking Lias appear healthy at the blastocyst stage, but their development is retarded globally by 7.5 days postcoitum (dpc), and all the null embryos die before 9.5 dpc. Supplementing the diet of heterozygous mothers with LA (1.65 g/kg of body weight) during pregnancy fails to prevent the prenatal deaths of homozygous embryos. Thus, endogenous LA synthesis is essential for developmental survival and cannot be replaced by LA in maternal tissues and blood.R-␣-Lipoic acid (6,8-thioctic acid) (LA) is a crucial cofactor that is required for the activity of the multienzyme complexes involved in the decarboxylation of ␣-ketoacids, important steps in energy metabolism. These complexes include pyruvate dehydrogenase complex (PDC), ␣-ketoglutarate dehydrogenase complex, branched chain ␣-ketoacid dehydrogenase complex (32), and a glycine cleavage system (11). LA is covalently attached via an amide bond to specific lysine residues of the E2 subunits of these complexes. LA is universally present in prokaryotes and eukaryotes (28), and previous investigations have shown that it is synthesized by lipoic acid synthase from octanoic acid and a sulfur source (23,25). Mouse lipoic acid synthase is encoded by the nuclear gene Lias.LA, one of the most potent natural antioxidants, has received considerable attention as a general dietary supplement for the past 15 years (3). Many lines of evidence have shown that both LA and its reduced form, dihydrolipoic acid (DHLA), have multifunctional antioxidant activities with the following characteristics (29). First, LA/DHLA are amphiphilic and readily cross the blood-brain barrier and cell membranes. Second, LA/DHLA possess metal-chelating activity. Third, LA is reduced to DHLA by several antioxidant enzymes that are expressed constitutively in most types of cells. In addition, because of its strong negative redox potential, DHLA can recycle other antioxidants, such as vitamin C, vitamin E, glutathione, coenzyme Q10, and ubiquinone (14,15,21,29,33).A growing body of evidence implicates oxidative stress as an important pathogenic element in a variety of diseases, including atheroscle...

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Oxidative stress and atherosclerosis

Cited by 83 publications

References 52 publications

Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase

Adiponectin inhibits palmitate-induced apoptosis through suppression of reactive oxygen species in endothelial cells: involvement of cAMP/protein kinase A and AMP-activated protein kinase

Gamma-glutamyltransferase to Determine Cardiovascular Risk: Shifting the Paradigm Forward

Endogenous Production of Lipoic Acid Is Essential for Mouse Development

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