Arduini A, Holme S, Sweeney J D, Dottori S, Sciarroni A F, Calvani M
Department of Sciences, University G. D'Annunzio, Pescara, Italy.
Transfusion. 1997 Feb;37(2):166-74. doi: 10.1046/j.1537-2995.1997.37297203519.x.
The role of L-carnitine (LC) as the requisite carrier of long-chain fatty acids into mitochondria is well established. Human red cells (RBCs), which lack mitochondria, possess a substantial amount of LC and its esters. In addition, carnitine palmitoyl transferase, an enzyme that catalyzes the reversible transfer of the acyl moiety from acyl-coenzyme A to LC is found in RBCs. It has recently been shown that LC and carnitine palmitoyl transferase play a major role in modulating the pathway for the turnover of membrane phospholipid fatty acids in intact human RBCs, and that LC improved the membrane stability of RBCs subjected to high shear stress. RBC membrane lesions occur during storage at 4 degrees C; this study investigated whether the addition of LC (5 mM) to a standard RBC preservative solution (AS-3) affected cellular integrity with 42 days' storage.
A paired (n = 10) crossover design was used for RBCs stored in AS-3 with and without LC. Both in vitro RBC properties reflective of metabolic and membrane integrity and in vivo measures of cell viability (24-hour percentage of recovery and circulating lifespan) were measured at the end of the storage. In addition, the turnover of membrane phospholipid and long-chain acylcarnitine fatty acids and the carnitine content of control and LC-stored RBCs were measured.
It was shown that LC was irreversibly taken up by RBCs during storage, with a fourfold increase at 42 days. Furthermore, as found by the use of radiolabeled palmitate, the stored RBCs were capable of generating long-chain acylcarnitine. The uptake of LC during storage was associated with less hemolysis and higher RBC ATP levels and by a significantly greater in vivo viability for LC-stored RBCs than for control-stored RBCs: a mean 24-hour percentage of recovery of 83.9 +/- 5.0 vs. 80.1 +/- 6.0 percent and a mean lifespan of 96 +/- 11 vs. 86 +/- 14 days, respectively (p < 0.05).
A beneficial effect of the addition of LC to RBCs stored at 4 degrees C was evident. This effect may be related to both biophysical and metabolic actions on the cell membrane.
左旋肉碱(LC)作为长链脂肪酸进入线粒体的必需载体,其作用已得到充分证实。缺乏线粒体的人类红细胞(RBC)含有大量的LC及其酯类。此外,红细胞中存在肉碱棕榈酰转移酶,该酶催化酰基部分从酰基辅酶A可逆地转移至LC。最近的研究表明,LC和肉碱棕榈酰转移酶在调节完整人类红细胞膜磷脂脂肪酸周转途径中起主要作用,并且LC可改善经受高剪切应力的红细胞的膜稳定性。红细胞膜损伤在4℃储存期间发生;本研究调查了在标准红细胞保存液(AS-3)中添加LC(5 mM)是否会影响42天储存期内的细胞完整性。
采用配对(n = 10)交叉设计,对在含和不含LC的AS-3中储存的红细胞进行研究。在储存结束时,测量反映代谢和膜完整性的体外红细胞特性以及细胞活力的体内指标(24小时恢复百分比和循环寿命)。此外,还测量了对照和LC储存红细胞的膜磷脂和长链酰基肉碱脂肪酸的周转以及肉碱含量。
结果表明,红细胞在储存期间不可逆地摄取LC,在42天时增加了四倍。此外,通过使用放射性标记的棕榈酸发现,储存后的红细胞能够生成长链酰基肉碱。储存期间LC的摄取与较少的溶血和较高的红细胞ATP水平相关,并且与对照储存的红细胞相比,LC储存的红细胞在体内具有显著更高的活力:平均24小时恢复百分比分别为83.9±5.0%和80.1±6.0%,平均寿命分别为96±11天和86±14天(p < 0.05)。
在4℃储存的红细胞中添加LC具有明显的有益作用。这种作用可能与对细胞膜的生物物理和代谢作用有关。