Regulation of reactive oxygen species (ROS) production by C18 fatty acids in Jurkat and Raji cells

Cury-Boaventura, Maria Fernanda; Curi, Rui

doi:10.1042/cs20040281

Cited by 72 publications

(43 citation statements)

References 77 publications

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“…Our results showing that vitamin C and NAC inhibit the stimulatory effect of LA on LOX-1 protein expression clearly identify endothelial LOX-1 as a novel oxidative stress-sensitive target for LA. In agreement with previous studies (36,37), we found that NADPH oxidase inhibitors prevented LA-induced protein expression, thus indicating that NADPH oxidase is one of the enzymatic superoxide sources activated by LA. Considering the potential key role of LOX-1 in ED, these results further support the concept that oxidative stress may constitute an important mechanism responsible for LA-mediated ED.…”

Section: Discussionsupporting

confidence: 81%

Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells

Maingrette

Renier

2005

Diabetes

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Results from in vitro studies suggest that selected fatty acids, and especially linoleic acid (LA), can elicit endothelial dysfunction (ED). Because LA is increased in all LDL subfractions in patients with type 2 diabetes, this alteration may contribute to ED associated with diabetes. Lectin-like oxidized LDL receptor-1 (LOX-1) is the major endothelial receptor for oxidized LDL (oxLDL), and uptake of oxLDL through LOX-1 induces ED. To evaluate whether LA may contribute to the upregulation of endothelial LOX-1 in diabetes, we studied the effect of LA on LOX-1 expression in cultured human aortic endothelial cells ( E ndothelial dysfunction (ED), a characteristic feature of early-state atherosclerosis, is well documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes (1,2). Critical factors that may induce activation and injury to the endothelium in the diabetic state include oxidized LDL (oxLDL) (3) and selected unsaturated fatty acids, such as linoleic acid (LA) (4). One potential key determinant of oxLDL-induced ED is lectin-like oxidized LDL receptor-1 (LOX-1), a newly identified limiting factor for oxLDL uptake by endothelial cells (5). Data showing that LOX-1 expression is enhanced by proatherogenic factors relevant to human diabetes, including oxLDL (6), high glucose (7), advanced glycation end products (8), and C-reactive protein (9), and is upregulated in endothelium and aortas of diabetic animals (8) support a role of this receptor in the pathogenesis of diabetic vascular dysfunction. Substantial amounts of data have been accumulated to show that LA is a pro-oxidative and proinflammatory molecule (10 -12) that can induce endothelial cell activation and dysfunction. These data and the observation that patients with type 2 diabetes show increased concentrations of LA in all LDL subfractions (13) support the significance of this fatty acid in ED associated with diabetes. In the present study, we investigated the role of LA in the regulation of endothelial LOX-1, the molecular mechanisms involved in this effect, and the role of LOX-1 in LA-induced oxLDL uptake by endothelial cells. RESEARCH DESIGN AND METHODS

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Section: Discussionsupporting

confidence: 81%

Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells

Maingrette

Renier

2005

Diabetes

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“…This time course fits with those of previous works (37)(38)(39), which reported early ROS production within 1 or 2 h after postprandial hypertriglyceridemia or after fatty acid in vitro exposure in circulating leukocytes or in lymphocytederived and pancreatic cell lines, respectively. Thus, lipids can rapidly stimulate elevation of intracellular ROS levels in numerous cell populations.…”

Section: Diabetes Vol 56 January 2007supporting

confidence: 78%

Role for Mitochondrial Reactive Oxygen Species in Brain Lipid Sensing

Bénani¹,

Troy²,

Carmona³

et al. 2007

Diabetes

122

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The ability for the brain to sense peripheral fuel availability is mainly accomplished within the hypothalamus, which detects ongoing systemic nutrients and adjusts food intake and peripheral metabolism as needed. Here, we hypothesized that mitochondrial reactive oxygen species (ROS) could trigger sensing of nutrients within the hypothalamus. For this purpose, we induced acute hypertriglyceridemia in rats and examined the function of mitochondria in the hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial respiration in the ventral hypothalamus together with a transient production of ROS. Cerebral inhibition of fatty acids-CoA mitochondrial uptake prevented the hypertriglyceridemia-stimulated ROS production, indicating that ROS derived from mitochondrial metabolism. The hypertriglyceridemia-stimulated ROS production was associated with change in the intracellular redox state without any noxious cytotoxic effects, suggesting that ROS function acutely as signaling molecules. Moreover, cerebral inhibition of hypertriglyceridemia-stimulated ROS production fully abolished the satiety related to the hypertriglyceridemia, suggesting that hypothalamic ROS production was required to restrain food intake during hypertriglyceridemia. Finally, we found that fasting disrupted the hypertriglyceridemia-stimulated ROS production, indicating that the redox mechanism of brain nutrient sensing could be modulated under physiological conditions. Altogether, these findings support the role of mitochondrial ROS as molecular actors implied in brain nutrient sensing. Diabetes 56: 152-160, 2007T he long-term maintenance of the body's energy homeostasis is a complex biological process achieved by numerous complementary mechanisms that imply sensor systems of fuel availability located in both peripheral and central sites. The hypothalamus in the central nervous system is a primary site of integration of nutritional information, which includes neural inputs as well as circulating metabolic signals, i.e., glucose or fatty acids (1,2). In turn, the hypothalamus elicits appropriate behavioral and metabolic responses to counterbalance any changes in the energy status.Previous studies have already shown that an overload of systemic lipids could stimulate activity of specific hypothalamic neurons (3) and modulate expression of neuropeptides, the key effectors of the hypothalamus (3-6), which leads to rapid or more delayed changes in peripheral metabolism. Moreover, chronic elevation of lipids may alter the hepatic sensitivity to insulin through their direct effect on the central nervous system (7). Recent findings (8) indicate that circulating lipids can directly act as signaling molecules, informing the hypothalamus about the body's metabolic status. Accordingly, it has been shown (9) that intracerebroventricular administration of long-chain fatty acids inhibited food intake and stimulated peripheral energy storage.One of the current challenges is to define the way fatty acids control neural activity within the hypotha...

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“…Furthermore, it promotes apoptosis through interfering with mitochondrial oxidative phosphorylation [36] and influencing the permeability of the mitochondrial membrane via Bax [37][38][39]. Oleic acid has also been described to increase the production of reactive oxygen species [38,40,41] and to inhibit the activation of NF-κB and thereby lead to increased apoptosis [42]. Moreover, oleic acid leads to p53-dependent apoptosis in Jurkat-cells [43] and it has been shown to activate peroxisome proliferator activated receptors which again results in increased cell death [44][45][46][47].…”

Section: Discussionmentioning

confidence: 99%

Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells

et al. 2006

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Unsaturated fatty acids with special structural features have been shown to activate serine/threonine protein phosphatase type 2C (PP2C) isoforms alpha and beta at physiological Mg(2+)-concentrations in vitro. These compounds also induce apoptosis in neuronal and endothelial cells. In this study we further analysed this striking correlation and tried to elucidate whether or not there is a causative relationship between activation of PP2C and induction of apoptosis. We employed RNA interference to simultaneously knock down PP2Calpha and PP2Cbeta in SH-SY5Y cells or HUVECs, respectively. This downregulation was transient. Treatment of SH-SY5Y cells or HUVECs with oleic acid (18:1,cis-Delta(9)) caused apoptosis in a time- and concentration-dependent manner. In both cases, cells with reduced PP2C-levels were less susceptible to oleic acid-induced cell damage. In conclusion, our results demonstrate that PP2C activation by unsaturated fatty acids actually causes apoptosis in neuronal and endothelial cells.

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Regulation of reactive oxygen species (ROS) production by C18 fatty acids in Jurkat and Raji cells

Cited by 72 publications

References 77 publications

Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells

Linoleic Acid Increases Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Expression in Human Aortic Endothelial Cells

Role for Mitochondrial Reactive Oxygen Species in Brain Lipid Sensing

Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells

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