New approach to modulate retinal cellular toxic effects of high glucose using marine epa and dha

Nutrition & Metabolism

Patrice Rat¹  Roxane Fagon²  Violaine de la Tourrette²  Mélody Dutot² 

[1] Laboratoire de Chimie et Toxicologie Analytique et Cellulaire, Faculté de Pharmacie, Université Paris Descartes, Paris, France;Yslab, Quimper, France

关键词: Caveolin-1;    Oxidative stress;    Omega-3;    Inflammation;    Glucose;   

Others  :  821188
DOI  :  10.1186/1743-7075-8-39

 received in 2011-04-11, accepted in 2011-06-16,  发布年份 2011

【 摘 要 】

Background

Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE) cells.

Methods

Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM) for 48 hours. Cellular responses were compared to normal glucose (5 mM): intracellular redox status, reactive oxygen species (ROS), mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography.

Results

Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil.

Conclusion

Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.

【 授权许可】

   
2011 Dutot et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]World Health Organization: Causes of blindness and visual impairment. Diabetic retinopathyAccessed March, 2010
• [2]Engerman RL, Kern TS: Hyperglycemia as a cause of diabetic retinopathy. Metabolism 1986, 35:20-23.
• [3]Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL, Klein R: Diabetic retinopathy. Diabetes Care 2003, 26:226-229.
• [4]Madsen-Bouterse SA, Kowluru RA: Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Rev Endocr Metab Disord 2008, 9:315-327.
• [5]Kowluru RA, Koppolu P, Chakrabarti S, Chen S: Diabetes-induced activation of nuclear transcriptional factor in the retina, and its inhibition by antioxidants. Free Radic Res 2003, 37:1169-1180.
• [6]Guha M, Bai W, Nadler JL, Natarajan R: Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways. J Biol Chem 2000, 275:17728-17739.
• [7]Miyamoto K, Khosrof S, Bursell SE, Rohan R, Murata T, Clermont AC, Aiello LP, Ogura Y, Adamis AP: Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci USA 1999, 96:10836-10841.
• [8]Tadayoni R, Paques M, Gaudric A, Vicaut E: Erythrocyte and leukocyte dynamics in the retinal capillaries of diabetic mice. Exp Eye Res 2003, 77:497-504.
• [9]Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP: A central role for inflammation in the pathogenesis of diabetic retinopathy. Faseb J 2004, 18:1450-1452.
• [10]Schnebelen C, Viau S, Gregoire S, Joffre C, Creuzot-Garcher CP, Bron AM, Bretillon L, Acar N: Nutrition for the eye: different susceptibility of the retina and the lacrimal gland to dietary omega-6 and omega-3 polyunsaturated fatty acid incorporation. Ophthalmic Res 2009, 41:216-224.
• [11]Schnebelen C, Gregoire S, Pasquis B, Joffre C, Creuzot-Garcher CP, Bron AM, Bretillon L, Acar N: Dietary n-3 and n-6 PUFA enhance DHA incorporation in retinal phospholipids without affecting PGE(1) and PGE (2) levels. Lipids 2009, 44:465-470.
• [12]Dutot M, Liang H, Martin C, Rousseau D, Grynberg A, Warnet JM, Rat P: Per os administered refined olive oil and marine PUFA-rich oils reach the cornea: possible role on oxidative stress through caveolin-1 modulation. Nutr Metab (Lond) 2009, 6:48. BioMed Central Full Text
• [13]Said T, Dutot M, Christon R, Beaudeux JL, Martin C, Warnet JM, Rat P: Benefits and side effects of different vegetable oil vectors on apoptosis, oxidative stress, and P2X7 cell death receptor activation. Invest Ophthalmol Vis Sci 2007, 48:5000-5006.
• [14]Said T, Dutot M, Martin C, Beaudeux JL, Boucher C, Enee E, Baudouin C, Warnet JM, Rat P: Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter. Eur J Pharm Sci 2007, 30:203-210.
• [15]Linard A, Macaire J, Christon R: Phospholipid hydroperoxide glutathione peroxidase activity and vitamin E level in the liver microsomal membrane: effects of age and dietary alpha-linolenic acid deficiency. J Nutr Biochem 2001, 12:481-491.
• [16]Yuan Z, Feng W, Hong J, Zheng Q, Shuai J, Ge Y: p38MAPK and ERK promote nitric oxide production in cultured human retinal pigmented epithelial cells induced by high concentration glucose. Nitric Oxide 2009, 20:9-15.
• [17]Du Y, Miller CM, Kern TS: Hyperglycemia increases mitochondrial superoxide in retina and retinal cells. Free Radic Biol Med 2003, 35:1491-1499.
• [18]Turrens JF: Superoxide production by the mitochondrial respiratory chain. Biosci Rep 1997, 17:3-8.
• [19]Ott M, Gogvadze V, Orrenius S, Zhivotovsky B: Mitochondria, oxidative stress and cell death. Apoptosis 2007, 12:913-922.
• [20]Kashihara N, Haruna Y, Kondeti VK, Kanwar YS: Oxidative stress in diabetic nephropathy. Curr Med Chem 2010, 17:4256-4269.
• [21]Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G: Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 2001, 280:E745-751.
• [22]Krogh-Madsen R, Plomgaard P, Keller P, Keller C, Pedersen BK: Insulin stimulates interleukin-6 and tumor necrosis factor-alpha gene expression in human subcutaneous adipose tissue. Am J Physiol Endocrinol Metab 2004, 286:E234-238.
• [23]Bazan NG: Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends Neurosci 2006, 29:263-271.
• [24]Bazan NG: Neurotrophins induce neuroprotective signaling in the retinal pigment epithelial cell by activating the synthesis of the anti-inflammatory and anti-apoptotic neuroprotectin D1. Adv Exp Med Biol 2008, 613:39-44.
• [25]Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN: Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 2005, 102:7671-7676.
• [26]Nascimento FA, Barbosa-da-Silva S, Fernandes-Santos C, Mandarim-de-Lacerda CA, Aguila MB: Adipose tissue, liver and pancreas structural alterations in C57BL/6 mice fed high-fat-high-sucrose diet supplemented with fish oil (n-3 fatty acid rich oil). Exp Toxicol Pathol 2010, 62:17-25.
• [27]Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, Maulik N: Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/Akt/eNOS signalling pathway in diabetic myocardium. J Cell Mol Med 2008, 12:2350-2361.
• [28]Raikar LS, Vallejo J, Lloyd PG, Hardin CD: Overexpression of caveolin-1 results in increased plasma membrane targeting of glycolytic enzymes: the structural basis for a membrane associated metabolic compartment. J Cell Biochem 2006, 98:861-871.