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Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells.

Shen J, Shen S, Das UN, Xu G - Lipids Health Dis (2012)

Bottom Line: Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity.These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Clinical Visual Science, Tongji Eye institute, Tongji University School of Medicine, Shanghai, China.

ABSTRACT

Background: Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3). The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.

Methods: RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF) secretion were evaluated.

Results: Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA) and α-linolenic acid (ALA), while the saturated fatty acid, palmitic acid was ineffective. A dose-response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells.

Conclusions: These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

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Related in: MedlinePlus

Effects of the interactions of ALA with Zn2+on the fluorescence polarization and microviscocity of RF/6A cells.(A) fluorescence polarization (B) microviscocity. Concentrations of Zn2+ and ALA were 80 and 3.7115 μmol/L respectively. Data are mean ± S.D. *P < 0.05 and **P < 0.01 compared to control. #P < 0.05 and ##P < 0.01 compared to G-50. $P < 0.05 and $$P < 0.01 compared to G-20.
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Figure 4: Effects of the interactions of ALA with Zn2+on the fluorescence polarization and microviscocity of RF/6A cells.(A) fluorescence polarization (B) microviscocity. Concentrations of Zn2+ and ALA were 80 and 3.7115 μmol/L respectively. Data are mean ± S.D. *P < 0.05 and **P < 0.01 compared to control. #P < 0.05 and ##P < 0.01 compared to G-50. $P < 0.05 and $$P < 0.01 compared to G-20.

Mentions: It is known that the “fluidity”-the thermal motion of the lipid bilayer of cell membrane-can be measured using fluorescence polarization technique- will give an indication as to cell membrane viscosity. The use of a fluorescent hydrocarbon, 1,6-diphenyl-1,3,5-hexatriene (DPH), to obtain fluorescence polarization and microviscosity values of the lipid bilayer of membranes of RF/6A cells treated with glucose, EFAs and Zn was performed. It is clear from these results given in Figure 4 that glucose enhanced fluorescence polarization and microviscocity (20 and 50 mM; 50 mM > 20 mM) that reverted to normal by treatment with Zn2+ and ALA. ALA was more potent than Zn2+ in reverting enhanced fluorescence polarization and microviscocity changes induced by glucose. On the other hand, Zn2+ and ALA by themselves or when added together did not have any effect on fluorescence polarization and microviscocity of RF/6A cells.


Effect of essential fatty acids on glucose-induced cytotoxicity to retinal vascular endothelial cells.

Shen J, Shen S, Das UN, Xu G - Lipids Health Dis (2012)

Effects of the interactions of ALA with Zn2+on the fluorescence polarization and microviscocity of RF/6A cells.(A) fluorescence polarization (B) microviscocity. Concentrations of Zn2+ and ALA were 80 and 3.7115 μmol/L respectively. Data are mean ± S.D. *P < 0.05 and **P < 0.01 compared to control. #P < 0.05 and ##P < 0.01 compared to G-50. $P < 0.05 and $$P < 0.01 compared to G-20.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475048&req=5

Figure 4: Effects of the interactions of ALA with Zn2+on the fluorescence polarization and microviscocity of RF/6A cells.(A) fluorescence polarization (B) microviscocity. Concentrations of Zn2+ and ALA were 80 and 3.7115 μmol/L respectively. Data are mean ± S.D. *P < 0.05 and **P < 0.01 compared to control. #P < 0.05 and ##P < 0.01 compared to G-50. $P < 0.05 and $$P < 0.01 compared to G-20.
Mentions: It is known that the “fluidity”-the thermal motion of the lipid bilayer of cell membrane-can be measured using fluorescence polarization technique- will give an indication as to cell membrane viscosity. The use of a fluorescent hydrocarbon, 1,6-diphenyl-1,3,5-hexatriene (DPH), to obtain fluorescence polarization and microviscosity values of the lipid bilayer of membranes of RF/6A cells treated with glucose, EFAs and Zn was performed. It is clear from these results given in Figure 4 that glucose enhanced fluorescence polarization and microviscocity (20 and 50 mM; 50 mM > 20 mM) that reverted to normal by treatment with Zn2+ and ALA. ALA was more potent than Zn2+ in reverting enhanced fluorescence polarization and microviscocity changes induced by glucose. On the other hand, Zn2+ and ALA by themselves or when added together did not have any effect on fluorescence polarization and microviscocity of RF/6A cells.

Bottom Line: Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity.These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Clinical Visual Science, Tongji Eye institute, Tongji University School of Medicine, Shanghai, China.

ABSTRACT

Background: Diabetic retinopathy is a major complication of dysregulated hyperglycemia. Retinal vascular endothelial cell dysfunction is an early event in the pathogenesis of diabetic retinopathy. Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by docosahexaenoic acid (DHA, 22:6 ω-3) and eicosapentaenoic acid (EPA, 20:5 ω-3). The influence of dietary omega-3 PUFA on brain zinc metabolism has been previously implied. Zn2+ is essential for the activity of Δ6 desaturase as a co-factor that, in turn, converts essential fatty acids to their respective long chain metabolites. Whether essential fatty acids (EFAs) α-linolenic acid and linoleic acid have similar beneficial effect remains poorly understood.

Methods: RF/6A cells were treated with different concentrations of high glucose, α-linolenic acid and linoleic acid and Zn2+. The alterations in mitochondrial succinate dehydrogenase enzyme activity, cell membrane fluidity, reactive oxygen species generation, SOD enzyme and vascular endothelial growth factor (VEGF) secretion were evaluated.

Results: Studies showed that hyperglycemia-induced excess proliferation of retinal vascular endothelial cells can be abrogated by both linoleic acid (LA) and α-linolenic acid (ALA), while the saturated fatty acid, palmitic acid was ineffective. A dose-response study with ALA showed that the activity of the mitochondrial succinate dehydrogenase enzyme was suppressed at all concentrations of glucose tested to a significant degree. High glucose enhanced fluorescence polarization and microviscocity reverted to normal by treatment with Zn2+ and ALA. ALA was more potent that Zn2+. Increased level of high glucose caused slightly increased ROS generation that correlated with corresponding decrease in SOD activity. ALA suppressed ROS generation to a significant degree in a dose dependent fashion and raised SOD activity significantly. ALA suppressed high-glucose-induced VEGF secretion by RF/6A cells.

Conclusions: These results suggest that EFAs such as ALA and LA may have beneficial action in the prevention of high glucose-induced cellular damage.

Show MeSH
Related in: MedlinePlus