Yechiel E, Barenholz Y
J Biol Chem. 1985 Aug 5;260(16):9123-31.
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.
通过比较5 - 6日龄的细胞（“年轻细胞”）和14 - 15日龄的细胞（“老龄细胞”）发现，新生大鼠心脏心肌细胞的培养物会经历与年龄相关的重大变化。这包括：细胞形状从球形变为细长形；鞘磷脂和胆固醇水平/细胞分别增加100%和50%，而磷脂酰胆碱减少15 - 20%，总磷脂含量几乎没有变化。细胞总蛋白含量增加50%，而DNA含量保持恒定。代表大多数亚细胞器的七种标记酶的比活性增加。搏动率从160±20次/分钟降至20±20次/分钟。上述所有与年龄相关的变化都受到细胞极性脂质组成改变的影响。添加到老龄细胞生长培养基中的卵磷脂酰胆碱小单层囊泡可作为卵磷脂酰胆碱的供体进入细胞，并作为细胞鞘磷脂和胆固醇的受体。鞘磷脂 - 磷脂交换可以通过仅在磷脂交换过程中起作用的卵磷脂酰胆碱/胆固醇混合物囊泡，或仅作为有效胆固醇受体的鞘磷脂小单层囊泡与胆固醇耗竭分开。此类实验表明，老龄细胞的主要反应是磷脂酰胆碱与鞘磷脂摩尔比的改变，而胆固醇水平的变化诱导的影响较小。因此，将磷脂酰胆碱与鞘磷脂摩尔比恢复到年轻细胞所示的值可使细胞功能和特征恢复到年轻细胞中的水平，这些功能和特征因细胞衰老而改变。这包括：搏动率增加回到160±20次/分钟，总蛋白水平降低以及七种标记酶的每DNA含量比活性降低，以及球形细胞形状重新出现。这些结果表明，膜脂质组成对细胞特性有重大影响，如随附论文（耶希尔，E.，巴伦霍尔兹，Y.，和赫尼斯，Y. I.（1985年）《生物化学杂志》260，9132 - 9136）所述，这可能是通过细胞膜的组织和动态介导的。
