Effects of Cataractogenesis on the CDP-Choline Pathway: Changes in ATP Concentration and Phosphocholine Synthesis during and after Exposure of Rat Lenses to Sugars in vitro and in vivo

Abstract

We measured choline influx and phosphorylation, ATP concentration ([ATP]), choline kinase activity and lens swelling during formation and partial reversal of sugar cataracts in rat lenses incubated with xylose or galactose and in lenses of galactosemic rats. [ATP] and phosphocholine (P-Cho) synthesis decreased about 60 and 40% after 4 h in normal rat lenses incubated up to 24 h in medium containing 30 mM xylose and partially recovered when the lenses were then removed from the xylose. Incubation with the somewhat less cataractogenic sugar galactose decreased P-Cho synthesis but had little effect on [ATP]. P-Cho synthesis decreased rapidly in the lenses of rats fed a 50% galactose diet, but began recovery by the third day on this diet. [ATP] decreased for at least 10 days during the galactose diet and did not recover, even with resumption of the control diet (50% starch) after 4 or 7 days. The results of in vitro and in vivo sugar cataractogenesis differed from each other in several respects, including effects on choline influx and the degree to which the changes were reversible. The in vitro and in vivo sugar cataracts, however, could both produce swelling and opacification of the lens and decreased P-Cho synthesis and [ATP]. Neither model caused a substantial change in the choline kinase activity (as measured in cell-free assays). The data did not generally support the hypothesis that decreased [ATP] causes decreased P-Cho synthesis.

Lipids and the ocular lens

“…Fatty acids carried by albumin are precursors for glycero-and sphingo-phospholipids ("Glycolipids" and 168 )]. Changes in the synthesis of phospholipids and their precursors during cataractogenesis have been investigated, but further studies are necessary to determine if the changes are related to natural differences in phospholipid metabolism or if these alterations are the result of damageinduced pathways that lead to membrane repair ( 179 ). The concentrations and rates of synthesis of phosphorylcholine and phosphoethanolamine, precursors of phospholipid synthesis decrease in cataractogenesis and cataractogenic stress (180)(181)(182)(183)(184)(185)(186)(187)(188)(189)(190)(191), and the kinetic properties and substrate specifi city of choline/ethanolamine kinase change during galactosemic cataractogenesis ( 192 ).…”

“…Increased phospholipid synthesis was reported to occur in an aldose-reductase inhibitor cataract model ( 185 ). The response of the lens to galactose insult is complicated by an initial decrease in phosphorylcholine synthesis followed by a recovery period ( 179 ). This recovery may be part of a broader response that controls phospholipid biosynthetic pathways and protects lenses against stresses.…”

Sphingolipids in human lens membranes: an update on their composition and possible biological implications

“…The bulk syntheses of PIs and PEs in rabbit and chick lenses (Vivekanandan and Lou, 1989;Zelenka, 1980Zelenka, , 1983, PCs and PEs in rat and primate lenses (Desouky et al, 1992;Ekambaram and Jernigan, 1994;Jernigan et al, 1981Jernigan et al, , 1993Jernigan and Zigler, 1989;Liu et al, 2003;Zelenka and Jernigan, 1982), and also plasmalogens in rat lens epithelial cells (Thai et al, 1999) have been addressed. The lower contents and slower net production of phosphorylcholines (the common headgroup of PCs, SMs and DHSMs) in primate lenses relative to rat lenses has been reported (Jernigan and Zigler, 1989).…”

Effects of Cataractogenesis on the CDP-Choline Pathway: Increased Phospholipid Synthesis in Lenses from Galactosemic Rats and 13/N Guinea Pigs

“…These effects include decreased lenticular concentrations of both of these intermediates, as well as decreased synthesis and increased leakage [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] . Although most other previous studies did not measure the synthesis of the fi nal products of the pathway, PtdCho and PtdEtn, Lou et al [22] reported that PtdCho synthesis was greater in lenses from diabetic rats than in control lenses.…”