Effect of dietary fat and environmental lighting on the phospholipid molecular species of rat photoreceptor membranes

doi:10.1016/S0014-4835(05)80111-3

Experimental Eye Research

Volume 60, Issue 3, March 1995, Pages 291-306

https://doi.org/10.1016/S0014-4835(05)80111-3 Get rights and content

We have previously shown that retinas of albino rats adapt to bright cyclic light (500–800 lx) by lowering the levels of docosahexaenoic acid (22:6n-3) in their rod outer segment (ROS) phospholipids. In the present study, we addressed the role of dietary fat in this process. Pregnant rats were kept in 1 lx or 250 lx cyclic illuminance (12L:12D) and fed diets containing 10% (by weight) of either hydrogenated coconut oil (COC, no n-3 or n-6 fatty acids), linseed oil (LIN, n-3 and n-6 fatty acids), or safflower oil (SAF, only n-6 fatty acids), starting 4 days before delivery. Pups were weaned at 3 weeks of age and continued on the same diet and light regime. At 12 weeks of age, 3 or 4 animals in each diet-light group were killed and the remaining animals were stressed continuously with 2000 lx light for 24 hr and then kept in 1 lx cyclic light for 10 days. Fatty acids and phospholipid molecular species (PLMS) of ROS membranes were determined. For prestressed groups, those animals fed the LIN diet had high levels of 22:6n-3 and PLMS containing 22:6n-3, with little 22:5n-6. Compared to the LIN group, the COC and SAF groups had lower levels of 22:6n-3- and 22:6n-3)-containing PLMS and higher levels of 22:5n-6 and molecular species containing 22:5n-6, such as 22:5n-6/22:6n-3, 16:0/22:5n-6 and 18:0/22:5n-6. Within each dietary group, animals raised in 250 lx cyclic illuminance had lower levels of 22:6n-3 and 22:5n-6 compared to those raised at 1 lx. This light effect was greater for 22:6n-3 in the LIN group than for 22:5n-6 in the SAF group. After the acute light stress, those animals raised in 1 lx showed dramatic reduction in PLMS containing 22:6 n-3 and 22:5n-6, especially polyenoic species such as 22:6n-3/22:6n-3 in the LIN group and 22:5n-6/22:6n-3 in the COC and SAF groups. In contrast, animals raised in 250 lx showed much smaller changes. These results demonstrate that: (1) the fatty acid and PLUMs compositions of rat ROS can be dramatically altered when pregnant animals are fed diets devoid of n-3 and/or n-6 essential fatty acids; (2) the level of 22:5n-6 and 22:6n-3 in ROS phospholipids is significantly affected by the level of cyclic rearing illuminance and (3) acute light stress has a dramatic effect on ROS PUFA in dim cyclic reared rats compared to those raised in bright cyclic light.

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Similarly, young rats fed 18:3n-3 deficient diets have depressed levels of DHA in ROS and elevated docosapentaneoic acid (22:5n-6), which replaces DHA during linolenic acid deficiency (Tinoco, 1982). In numerous studies, DHA-depleted rats were found to exhibit reduced retinal light damage (Organisciak et al., 1987, 1996; Bush et al., 1991, 1994; Koutz et al., 1995; Wiegand et al., 1995), although the reasons are not entirely clear. Bush et al. (1994) suggest that protection is attributable to reduced photon absorption by rhodopsin and to a slower than normal rate of rhodopsin regeneration.
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Moreover, the presence of DHA at all positions, compared with only one position, was shown to increase the oxidizability of lipids such as triacylglycerols and PC (58). In rat photoreceptor membranes, diDHA PL molecular species are selectively decreased under oxidative stress related to light (59). Several studies have reported a correlation between vitamin E levels and cellular redox status (60, 61).
Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid (PL) preferentially found in late endosomal membranes, where it forms specialized lipid domains. Recently, using cultured macrophages treated with anti-BMP antibody, we showed that BMP-rich domains are involved in cholesterol homeostasis. We had previously stressed the high propensity of BMP to accumulate docosahexaenoic acid (DHA), compared with other PUFAs. Because phosphatidylglycerol (PG) was reported as a precursor for BMP synthesis in RAW macrophages, we examined the effects of PG supplementation on both FA composition and amount of BMP in this cell line. Supplementation with dioleoyl-PG (18:1/18:1-PG) induced BMP accumulation, together with an increase of oleate proportion. Supplementation with high concentrations of didocosahexaenoyl-PG (22:6/22:6-PG) led to a marked enrichment of DHA in BMP, resulting in the formation of diDHA molecular species. However, the amount of BMP was selectively decreased. Similar effects were observed after supplementation with high concentrations of nonesterified DHA. Addition of vitamin E prevented the decrease of BMP and further increased its DHA content. Supplementation with 22:6/22:6-PG promoted BMP accumulation with an enhanced proportion of 22:6/22:6-BMP. DHA-rich BMP was significantly degraded after cell exposure to oxidant conditions, in contrast to oleic acid-rich BMP, which was not affected. Using a cell-free system, we showed that 22:6/22:6-BMP is highly oxidizable and partially protects cholesterol oxidation, compared with 18:1/18:1-BMP. Our data suggest that high DHA content in BMP led to specific degradation of this PL, possibly through the diDHA molecular species, which is very prone to peroxidation and, as such, a potential antioxidant in its immediate vicinity.
Different mechanisms of saturated versus polyunsaturated FFA-induced apoptosis in human endothelial cells
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However, this does not appear very likely, given that membrane incorporation of FFAs does not correlate with endothelial apoptosis and that HUVECs and HRECs comparably incorporate linoleic acid (19 nmol/103 cells vs. 13 nmol/103 cells) while completely differing in their apoptotic response. Particularly, insusceptibility of HRECs to PUFA-induced apoptosis might result from an adaptive mechanism of retinal endothelial cells to their highly unsaturated environment in vivo (27, 28): the retina possesses specific retinal fatty acid binding proteins that act as anti-oxidants by preferably binding PUFAs (29, 30). Moreover, the phenomenon of HREC “resistance” to and HAEC“susceptibility” to PUFA-induced cell death could provide one explanation for the association between high plasma FFAs and (diabetic) retinopathy, which is less obvious than the relationship between chronic elevation of FFAs in diabetes and/or visceral obesity and atherosclerosis (1, 31, 32).
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Retinal fatty acid binding protein reduce lipid peroxidation stimulated by long-chain fatty acid hydroperoxides on rod outer segments
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In the present study we have investigated the effect of partially purified retinal fatty acid binding protein (FABP) against nonenzymatic lipid peroxidation stimulated by hydroperoxides derived from fatty acids on rod outer segment (ROS) membranes. Linoleic acid hydroperoxide (LHP), arachidonic acid hydroperoxide (AHP) and docosahexaenoic acid hydroperoxide (DHP) were prepared from linoleic acid, arachidonic acid and docosahexaenoic acid, respectively, by means of lipoxidase. ROS membranes were peroxidized using an ascorbate–Fe⁺² experimental system. The effect on the peroxidation of ROS containing different amounts of lipid hydroperoxides (LOOH) was studied; ROS deprived of exogenously added LOOH was utilized as control. The degradative process was measured simultaneously by determining chemiluminescence and fatty acid composition of total lipids isolated from ROS. The addition of hydroperoxides to ROS produced a marked increase in light emission. This increase was hydroperoxide concentration-dependent. The highest value of activation was produced by DHP. The decrease percentage of the more polyunsaturated fatty acids (PUFAs) (20:4 n6 and 22:6 n3) was used to evaluate the fatty acid alterations observed during the process. We have compared the fatty acid composition of total lipids isolated from native ROS and peroxidized ROS that were incubated with and without hydroperoxides. The major difference in the fatty acid composition was found in the docosahexaenoic acid content, which decreased by 45.51±1.07% in the peroxidized group compared to native ROS; the decrease was even higher, 81.38±1.11%, when the lipid peroxidation was stimulated by DHP. Retinal FABP was partially purified from retinal cytosol. Afterwards, we measured its effect on the reaction of lipid peroxidation induced by LOOH. As a result, we observed a decrease of chemiluminescence (inhibition of lipid peroxidation) when adding increasing amounts (0.2 to 0.6 mg) of retinal FABP to ROS. The inhibitory effect reaches its highest value in the presence of DHP (41.81±10.18%). Under these conditions, bovine serum albumin (BSA) produces a smaller inhibitory effect (20.2±7.06%) than FABP.
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Effect of dietary fat and environmental lighting on the phospholipid molecular species of rat photoreceptor membranes

J. Lipid Res.

Arch. Biochem. Biophys.

Biochim. Biophys. Acta

Vision Res.

Arch. Biochem. Biophys.

Exp. Eye Res.

Exp. Neurol.

J. Chromatogr.

J. Nutr.

Exp. Eye Res.

Exp. Eye Res.

J. Lipid Res.

Biochim. Biophys. Acta

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

Exp. Eye Res.

J. Lipid Res.

Prog Lipid Res.

Docosahexaenoic acid is the preferred dietary n-3 fatty acid for the development of the brain and retina

Pediatr. Res.

Structural and metabolic heterogeneity of rat liver glycerophosphatidase

European J. Biochem.

Membrane fatty acids associated with the electrical response in visual excitation

Science

Retinal development in very-low-birth-weight infants fed diets differing in omega-3 fatty acids

Invest. Ophthalmol. Vis. Sci.

A rapid method of total lipid extraction and purification

Can. J. Biochem. Physiol.

Chemistry and metabolism of lipids in the vertebrate retina

Prog. Lipid Res.

Effect of essential fatty acid deficiency on the fatty acid composition, morphology, and electroretinographic response of the retina

Invest. Ophthalmol.

Retinal pigment epithelial cells play a central role in the conservation of docosahexaenoic acid by photoreceptor cells after shedding and phagocytosis

Curr. Eye Res.

Ultrastructural and light microscopy autoradiography of [3H]DHA-containing phagosomes in the RPE

Invest. Ophthalmol. Vis. Sci.

Ultrastructural and light microscopy autoradiography of [³H]DHA-containing phagosomes in the RPE