Linoleic acid and antioxidants protect against DNA damage and apoptosis induced by palmitic acid

Beeharry, Neil; Lowe, Jillian E.; Hernandez, Alma Rosales; Chambers, Julie A.; Fucassi, Flavia; Cragg, Peter J.; Green, Michael H.L.; Green, Irene C.

doi:10.1016/s0027-5107(03)00134-9

Cited by 80 publications

(50 citation statements)

References 30 publications

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“…We clearly demonstrated using two different methods (FACS and image analysis) that PA induces growth arrest of PAV-1 cells. This biological effect was already observed in an insulin-secreting cell line, presenting important growth inhibition (48% of control growth) induced by 50 µM PA [52]. Kliewer et al [53] previously demonstrated that PPAR-α and -γ are activated by fatty acids including PA.…”

Section: Discussionmentioning

confidence: 71%

Growth Arrest and Decrease of α-SMA and Type I Collagen Expression by Palmitic Acid in the Rat Hepatic Stellate Cell Line PAV-1

Abergel¹,

Sapin

Dif

et al. 2006

Dig Dis Sci

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Liver fibrosis is characterized by an activation of hepatic stellate cells (HSC). During primary culture HSC evolve from a quiescent into an activated phenotype which is characterized by alpha-smooth muscle actin (alpha-SMA) up-regulation, increase in cell growth, and extracellular matrix secretion. HSC culture with trans-resveratrol can lead to deactivation of myofibroblast-like HSC. We used an HSC line, PAV-1, to check the role of retinol and palmitic acid in the deactivation process of HSC. Using mass and metabolic-based methods, Western blot and immunocytochemistry assays, we demonstrated that treatment with palmitic acid (75 muM) alone or in combination with retinol (2 muM) significantly decreased cell proliferation and alpha-SMA expression. We also established that the association of both compounds strongly decreased collagen type I expression. Our results suggest the potential use of palmitic acid alone or in combination with retinol to induce HSC deactivation.

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Section: Discussionmentioning

confidence: 71%

Growth Arrest and Decrease of α-SMA and Type I Collagen Expression by Palmitic Acid in the Rat Hepatic Stellate Cell Line PAV-1

Abergel¹,

Sapin

Dif

et al. 2006

Dig Dis Sci

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“…Preparation of FFAs-FFAs were prepared as described previously (23). Briefly, stock palmitic acid or methyl ester palmitic acid solution in methanol (80 mmol/liter) was conjugated to fatty acid-free bovine serum albumin in a 3:1 molar ratio at 37°C for at least 1 h prior to treatment.…”

Section: Methodsmentioning

confidence: 99%

“…2, A and B). Metabolism of palmitate has been shown to be required to elicit acetylCoA carboxylase down-regulation (30) and ␤-cell apoptosis (23). To test whether palmitate metabolism is mandatory to the regulation of Cx36 expression, INS-1E cells were treated with palmitic acid methyl ester, a nonmetabolizable analogue of palmitate that is not activated into a fatty acyl-CoA in the cytosol (31)(32)(33).…”

Section: Palmitate But Not Oleate or Linoleate Represses Cx36mentioning

confidence: 99%

ICER-1γ Overexpression Drives Palmitate-mediated Connexin36 Down-regulation in Insulin-secreting Cells

Allagnat

Alonso

Martín

et al. 2008

Journal of Biological Chemistry

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Channels formed by the gap junction protein connexin36 (Cx36) contribute to the proper control of insulin secretion. We investigated the impact of chronic hyperlipidemia on Cx36 expression in pancreatic ␤-cells. Prolonged exposure to the saturated free fatty acid palmitate reduced the expression of Cx36 in several insulin-secreting cell lines and isolated mouse islets. The effect of palmitate was fully blocked upon protein kinase A (PKA) inhibition by H89 and (Rp)-cAMP, indicating that the cAMP/PKA pathway is involved in the control of Cx36 expression. Palmitate treatment led to overexpression of the inducible cAMP early repressor (ICER-1␥), which bound to a functional cAMP-response element located in the promoter of the CX36 gene. Inhibition of ICER-1␥ overexpression prevented the Cx36 decrease, as well as the palmitate-induced ␤-cell secretory dysfunction. Finally, freshly isolated islets from mice undergoing a long term high fat diet expressed reduced Cx36 levels and increased ICER-1␥ levels. Taken together, these data demonstrate that chronic exposure to palmitate inhibits the Cx36 expression through PKA-mediated ICER-1␥ overexpression. This Cx36 down-regulation may contribute to the reduced glucose sensitivity and altered insulin secretion observed during the pre-diabetic stage and in the metabolic syndrome.The fine-tuning of insulin secretion in response to nutrient stimulation relies on a closely coordinated functioning of pancreatic ␤-cells. The cell-to-cell communication mediated by gap junction channels contributes to synchronization of ␤-cell clusters and has been demonstrated to be essential for the proper regulation of storage and release of insulin, both in vitro and in vivo (for review see Ref. 1). Gap junctions are specific membrane structures consisting of aggregates of intercellular channels interconnecting the cytoplasms of neighboring cells and providing them with a direct pathway for sharing ions, nutrients, and intracellular messengers. We and others (2-5) have demonstrated that only one connexin, the constitutive unit of these channels, is expressed in insulin-secreting cells, connexin36 (Cx36 2 for 36 kDa), and that this connexin plays a critical role in ␤-cell function. In addition, modulation of the Cx36 levels results in impaired glucose-induced insulin secretion, indicating that Cx36 must be expressed at a very precise level to maintain a normal insulin secretion (2, 6). Thus, changes in the Cx36 expression levels might impair ␤-cell function and hence be involved in the pathophysiology of diabetes mellitus.Type 2 diabetes partly ensues from ␤-cell failure to compensate for peripheral insulin resistance (for review see Ref. 7). Abnormalities in both glucose and lipid metabolism contribute to the pathogenesis of this condition and in particular to the inexorable decline of ␤-cell function (8, 9). Recently, we have demonstrated that long term exposure to a high concentration of glucose resulted in a reduced expression of Cx36 in insulinsecreting cells (10). Although hyperglycemia is und...

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“…Interestingly, palmitic acid, one of the most abundant fatty acids in the human diet and precursor of the widely studied 2-dDCB, itself causes oxidative DNA damage, DNA strand breaks, cell membrane damage, necrosis and apoptosis in vitro, and is positive in Comet and flow cytometric assays in the same dose range as 2-dDCB (Beeharry et al, 2003;de Sousa et al, 2005;Esteves et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Scientific Opinion on the Chemical Safety of Irradiation of Food

Flavourings¹

2011

EFSA Journal

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Irradiation (gamma rays, electrons or X-rays) is applied to foods for improving food safety and removing and reducing pests that are harmful to plants or plant products. As ionising radiation passes through food, it creates a trail of chemical transformations by primary and secondary radiolysis effects. The main reported radiolytic products are certain hydrocarbons and 2-alkylcyclobutanones produced from the major fatty acids in food, and some cholesterol oxides and furans. Most of these substances are also formed in food that has been subjected to other processing treatments and are thus not exclusively formed by irradiation. Furthermore, the quantities in which they occur in irradiated food are not significantly higher than those being formed in heat treatments. Since the last SCF opinion in 2003, several in vitro genotoxicity studies on irradiated foods have been published. The available data indicate that at least some 2-alkylcyclobutanones may induce DNA damage in vitro. No in vivo genotoxicity studies are available; however, a genotoxic hazard in humans is considered unlikely by the Panel in view of the plausible indirect mechanism underlying the genotoxicity of alkylcyclobutanones in vitro. Concerning other radiolytic products no new relevant toxicological studies have been reported. The weight of evidence from recent literature regarding biological effects supports the food classes and radiation doses specified in previous SCF opinion in 2003. The only new contrary evidence was indicated in publications on leukoencephalomyelopathy in cats which have been fed mainly or exclusively with highly irradiated feed. However a clear mechanistic explanation in terms of risk assessment has not been established. Considering that only a very limited quantity of food is irradiated in Europe currently, the Panel is of the view that there is not an immediate cause for concern. However, the relevance of the cats studies for human health should be clarified.

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Linoleic acid and antioxidants protect against DNA damage and apoptosis induced by palmitic acid

Cited by 80 publications

References 30 publications

Growth Arrest and Decrease of α-SMA and Type I Collagen Expression by Palmitic Acid in the Rat Hepatic Stellate Cell Line PAV-1

Growth Arrest and Decrease of α-SMA and Type I Collagen Expression by Palmitic Acid in the Rat Hepatic Stellate Cell Line PAV-1

ICER-1γ Overexpression Drives Palmitate-mediated Connexin36 Down-regulation in Insulin-secreting Cells

Scientific Opinion on the Chemical Safety of Irradiation of Food

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