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MC Yappert, R Estrada, I Vorobyov, M Rujoi, J Rudolph, D Borchman; Phospholipid Segregation In Mammalian Lens Membranes And Control Of Fiber Growth . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4636.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine phospholipid compositional differences in the plasma membrane of axial and lateral regions of the lens cortex and nucleus. Methods: A 2-mm diameter trephine was used to excise a cylindrical core along the optical axis of frozen porcine lenses. The top and bottom 1.5-mm segments of the core were pooled and labeled axial cortex (AC). The central portion (3 mm) of the core was defined as axial nucleus (AN). The outer and inner layers (2-3 mm thick) of the annulus surrounding the core were separated and denoted lateral cortex (LC) and lateral nucleus (LN), respectively. The lipids extracted from each fraction were analyzed by 31P NMR and MALDI-TOF/MS. Results: The compositional data obtained by NMR indicated a decrease in the content of phosphatidylcholines (PCs) from the LC (31%) to the AC (26% ), the LN (25%), and the AN (23%). Conversely, sphingomyelin (SM) increased from 15% (LC) to 21% (AC and LN) and 46% (AN). MALDI-TOF/MS results showed that for SMs, the relative content of SM(16:0) decreased from the LC to the AN, while those of SM(18:0) and SM(24:1) increased. The relative content of PCs with saturated acyl chains increased from the LC to the AN. Conclusion: The signaling roles of phospholipids and their metabolites have been demonstrated in other tissues. Specifically, diacylglycerol derived from PC promotes the activity of members of the protein kinase C (PKC) family, a group of enzymes involved in growth control. Ceramide and sphingosine, metabolites of SM, are potent inhibitors of PKC and induce growth arrest and apoptosis. We conclude that given the high levels of SM in the non-growing inner nucleus and of PC in the fast-growing lateral cortex, it is likely that phospholipids are not just passive constituents of lens plasma membranes but also relevant sources of signaling molecules that control fiber growth. Furthermore, compared to the lateral regions, the relative content of SM was higher in the axial core in which the terminal ends of the fibers are present. Therefore, we hypothesize that in order for the terminal ends to maintain their size, they must be in a state of growth arrest facilitated by the presence of SM and its metabolites. Conversely, the higher contents of PCs in the outer lateral cortex may contribute to the rapid elongation of the lateral sides of outer cortical fibers. We propose that the segregation of PCs and SMs influences the fate of lens cells by contributing to the regulation of their growth levels.
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