Relationships between membrane lipid composition and biological properties of rat myocytes. Effects of aging and manipulation of lipid composition.
56
Citation
56
Reference
10
Related Paper
Citation Trend
Abstract:
Abstract Cultures of newborn rat heart myocytes undergo major age-related alterations as demonstrated by comparing 5-6-day-old cells (young cells) and 14-15-day-old cells (old cells). This includes: changes from spherical to elongated shape; sphingomyelin and cholesterol level/cell increase by 100% and 50%, respectively, while the phosphatidylcholine is reduced by 15-20% with almost no change in content of total phospholipids. There is a 50% increase in total protein content/cell while DNA content remain constant. The specific activity of seven marker enzymes representing most subcellular organelles is increased. Beating rate is reduced from 160 +/- 20 to 20 +/- 20 beats min-1. All the above age-dependent alterations are affected by modification of cellular polar lipid composition. Small unilamellar vesicles of egg phosphatidylcholine added to the growth medium of old cells serve as donor of egg phosphatidylcholine to the cells and as acceptor of cellular sphingomyelin and cholesterol. Sphingomyelin-phospholipid exchange can be separated from cholesterol depletion either by using vesicles of egg phosphatidylcholine/cholesterol mixtures which serve only in the phospholipid exchange process, or by small unilamellar vesicles of sphingomyelin which act only as efficient cholesterol acceptors. Such experiments indicated that the major response of old cells is to alteration in the phosphatidylcholine to sphingomyelin mole ratio, while changes in the cholesterol level induce smaller effects. Thus, reversal of phosphatidylcholine to sphingomyelin mole ratio to the values shown by young cells reverse cellular functions and features which were altered by cell aging to levels found in young cells. This includes: increase in the beating rate back to 160 +/- 20, reduction in the total protein level and in the specific activity per DNA content of seven marker enzymes and reappearance of spherical cell shape. These results suggest that membrane lipid composition has major influence on cellular properties which as described in the accompanying paper (Yechiel, E., Barenholz, Y., and Henis, Y. I. (1985) J. Biol. Chem. 260, 9132-9136), may be mediated through the organization and dynamics of the cell membranes.Keywords:
Choline
Phosphocholine
Choline
Bovine milk
Choline kinase
Cite
Citations (210)
A-4, A-5 and HC-3 are experimental bis tertiary and quaternary amines which have been shown to be potent inhibitors of the sodium-dependent, high affinity choline uptake system. When incubated with neuroblastoma cells, experimental compounds A-4, A-5 and HC-3 inhibit choline metabolism. Over a 24-hr incubation, A-4, A-5 and HC-3 produced a significant decrease in total choline accumulation, choline incorporation into phospholipid and free choline content. However, despite decreases in choline incorporation into phospholipid, no change occurred in content of phosphatidylcholine. Treatment of cells with A-4, A-5 and HC-3 resulted in an increase in the incorporation of S-adenosyl-methionine into phosphatidylcholine. However, the incorporation of ethanolamine or serine into phosphatidylcholine was not increased. Phosphatidylcholine turnover was decreased in cells treated with A-4 and A-5. A-4, A-5 and HC-3 produce significant decreases in choline metabolism; however, the cells are able to maintain membrane integrity by decreasing turnover of phosphatidylcholine and increasing phosphatidylcholine synthesis through the methylation pathway. These studies suggest that the biological effects of A-4 and A-5 are independent of membrane perturbations.
Choline
Phosphocholine
Choline kinase
Betaine
Cite
Citations (1)
Choline
Cite
Citations (2)
Cite
Citations (28)
Choline
Phosphatidylethanolamine
Cite
Citations (5)
1. Injection of [Me-14C]choline into sheep indicated that the small amount of phosphatidylcholine present in abomasal digesta was largely (69%) of non-dietary or ruminal origin. 2. Long-term feeding of [Me-3H]choline to sheep produced insignificant labelling of plasma phosphatidylcholine, indicating that more than 99% of the choline body pool was of non-dietary origin. 3. In contrast, when rats were fed with [Me-3H]choline for similar periods, 18-54% of the tissue phosphatidylcholine was derived from dietary choline. 4. The loss of [14C]choline and 32P from the plasma phosphatidylcholine after a single injection of these isotopes indicated a markedly slower turnover of choline in the sheep compared with the rat. This observation, coupled with a lack of liver glycerophosphocholine diesterase, provides an explanation for the insensitivity of the sheep to an almost complete microbial destruction of dietary choline before alimentary-tract absorption.
Choline
Phosphocholine
Cite
Citations (49)
In six normal subjects we investigated the effects of oral phosphatidylcholine (lecithin) on the concentrations of plasma choline, erythrocyte choline, and choline-containing lipids. Plasma choline levels rose 1 hr after treatment and remained elevated for 8 hr, with peaks at 3 and 4 hr after phosphatidylcholine. Erythrocyte choline levels also rose, although the rise was slightly delayed relative to plasma choline. There was no change in the plasma choline-containing lipid concentration. These results demonstrate that, in normal subjects, oral phosphatidylcholine induces prolonged rises in plasma and erythrocyte choline concentrations and is therefore useful when such effects are desired. Clinical Pharmacology and Therapeutics (1982) 31, 483–487; doi:10.1038/clpt.1982.64
Choline
Blood plasma
Cite
Citations (19)
Choline
Egg lecithin
Cite
Citations (49)
Choline
Cite
Citations (12)