Comparative study of serine-plasmalogens in human retina and optic nerve: identification of atypical species with odd carbon chains

Abstract

This article is available online at http://www.jlr.org phospholipids and cholesterol esters, both playing structural functions without being related to energy metabolism ( 3 ). As elements of the nervous system, ocular tissues, such as the optic nerve and the neural retina, display similar composition ( 5-7 ). In mammalian cell membranes, phospholipids also comprise ether-linked species containing either an alkyl-ether or a vinyl-ether bond at the sn-1 position of glycerol ( 3,5,8 ). The vinyl-ether-linked species include a carbon-carbon double bond next to the ether linkage in comparison to the ether forms. Vinyl-ether bearing phospholipids are termed as plasmalogens and are found in numerous mammalian cell types, including the retina ( 9-11 ), mostly in the forms of phosphatidylcholines (PC) and phosphatidylethanolamines (PE). In plasmalogens, the sn-2 position of glycerol backbone is usually occupied by PUFAs, whereas the sn-1 position is linked to vinyl-ether moieties with 16 to 18 carbon. The biological functions of plasmalogens are still unclear, although it has been reported that the presence of plasmalogens in membrane affects its fl uidity and fusion ( 8 ). Due to the high PUFA content of plasmalogens, they are also considered as reservoirs of PUFAs, which can be used by a plasmalogen-specifi c phospholipase A2 (iPLA2) ( 12, 13 ) to liberate free fatty acids in order to be further metabolized into second messenger molecules, such as prostaglandins and thromboxanes ( 14, 15 ). The alteration of cellular plasmalogen content has been associated with several human disorders and diseases, such as rhizomelic chondrodysplasia punctata Type 2, Alzheimer's disease, Down syndrome, Zellweger syndrome, and primary open-angle glaucoma ( 8,(16)(17)(18).Although PC and PE are the major phospholipid classes containing plasmalogens, vinyl-ether bearing phospholipids can also appear in the form of phosphatidylserine (PS). The nervous system is an organ with the second highest concentration of lipids, only exceeded by adipose tissue. Nervous tissues contain about 50 to 60% of their dry weight as lipids, and approximately 35 to 40% of these lipids are polyunsaturated fatty acids (PUFAs) ( 1-4 ). The majority of these lipids appear as PUFA-rich-membrane

Phosphatidylserine synthase 2: high efficiency for synthesizing phosphatidylserine containing docosahexaenoic acid

“…Our fi nding that purifi ed PSS2 is capable of converting PE plasmalogen to PS plasmalogen is intriguing in that PS plasmalogen is rarely found in mammalian tissues, although a recent report indicated the presence of PS plasmalogens in the retina and the optic nerve ( 42 ). Due to the unique double bond of vinyl ether group, plasmalogens are reported to function as an antioxidant by scavenging reactive oxygen species, thereby protecting polyunsaturated fatty acids, including DHA, from oxidative stress and preserving membrane function ( 43 ).…”

Recent Advances in Shotgun Lipidomics and Their Implication for Vision Research and Ophthalmology

“…50-52 Very recently, red blood cell lipid profiles were found to be reflective of optic nerve lipid changes in glaucoma. 53,54 The comprehensive analyses of aqueous humor and trabecular meshwork by our group have shown the absence of some specific lipids such as PC22:6/22:6 in the trabecular meshwork (Bhattacharya, SK, unpublished observation), thus demonstrating parallel between systemic (blood) of some lipid entities and localized tissue. 53,54 Most of these findings are yet in infancy.…”

Phosphatidylserine in the brain: Metabolism and function

“…These alkyl ethers contain saturated (16:0 and 18:0) and monounsaturated (18:1) hydrocarbon chains. Studies using liquid chromatography combined with tandem mass spectrometry also demonstrate the presence of serine plasmalogens in postmortem samples of human retina and optic nerve obtained from males and females between the ages of 72 and 94 years [57]. Polyunsaturated molecular species were present in the retinal serine plasmalogens.…”

“…Polyunsaturated molecular species were present in the retinal serine plasmalogens. The function of the retinal PS alkyl ethers and serine plasmalogens is unknown, but the more highly unsaturated molecular species are thought to be involved in retinal signaling [57]. …”