Hatch G M, Cao S G, Angel A
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Biochem J. 1995 Mar 15;306 ( Pt 3)(Pt 3):759-64. doi: 10.1042/bj3060759.
Biosynthesis of phosphatidylglycerol (PG) and cardiolipin (CL) were investigated in perfused hearts of diabetic rats 4 days or 28 days after streptozotocin injection. Sham-injected and insulin-treated diabetic rats were used as controls. In addition, another group of rats fasted for 54 h was examined. Isolated rat hearts from these groups were perfused for 30 min with [32P]P(i), and the radioactivity incorporated into PG and CL and their pool sizes were determined in heart ventricles. There was no difference in the amount of radioactivity incorporated into CL, PG or other phospholipids between all groups. In addition, the pool sizes of CL and other phospholipids were unaltered. However, a striking decrease in the pool size of PG was observed in both diabetic and fasted rats compared to sham- and insulin-treated controls at 4 days after streptozotocin injection. The decrease in PG mass in diabetic rats was rapid (within 24-48 h) and was localized to cardiac membranes. Diabetes did not affect the activity of the enzymes of PG and CL biosynthesis in the mitochondrial fraction, or phospholipase A activity in subcellular fractions prepared from rat heart homogenates. In addition, pulse-chase experiments confirmed that diabetes did not affect the rate of new PG or CL biosynthesis. Since radioactivity associated with PG was unaltered in continuous-pulse perfusion experiments, a calculated 1.8-fold increase in the specific radioactivity of cardiac PG was observed in the hearts of acute diabetic rats compared with controls. Since the radioactivity incorporated into PG and CL, and the rate of CL biosynthesis, were unaltered in diabetic-rat hearts compared with controls, new CL was probably synthesized from newly synthesized PG. We postulate the existence of distinct pools of PG in the heart, and that the pool of newly synthesized PG used for CL biosynthesis does not appear to mix immediately with the pre-existing pool of PG in the isolated intact rat heart.
在链脲佐菌素注射后4天或28天的糖尿病大鼠灌注心脏中，研究了磷脂酰甘油（PG）和心磷脂（CL）的生物合成。假注射和胰岛素治疗的糖尿病大鼠用作对照。此外，还检查了另一组禁食54小时的大鼠。用[32P]P(i)对这些组的离体大鼠心脏灌注30分钟，并测定心室中掺入PG和CL的放射性及其池大小。所有组之间掺入CL、PG或其他磷脂的放射性量没有差异。此外，CL和其他磷脂的池大小未改变。然而，与链脲佐菌素注射后4天的假注射和胰岛素治疗对照相比，糖尿病和禁食大鼠的PG池大小均显著降低。糖尿病大鼠中PG质量的降低迅速（在24 - 48小时内），且局限于心脏膜。糖尿病不影响线粒体部分中PG和CL生物合成酶的活性，也不影响从大鼠心脏匀浆制备的亚细胞部分中的磷脂酶A活性。此外，脉冲追踪实验证实糖尿病不影响新PG或CL生物合成的速率。由于在连续脉冲灌注实验中与PG相关的放射性未改变，与对照相比，急性糖尿病大鼠心脏中计算得出的心脏PG比放射性增加了1.8倍。由于与对照相比，糖尿病大鼠心脏中掺入PG和CL的放射性以及CL生物合成速率未改变，新的CL可能由新合成的PG合成。我们推测心脏中存在不同的PG池，并且用于CL生物合成的新合成PG池在离体完整大鼠心脏中似乎不会立即与预先存在的PG池混合。
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