Alessenko A, Chatterjee S
Department of Pediatrics, Johns Hopkins University, Baltimore, MD 21287-3654, USA.
Mol Cell Biochem. 1995 Feb 23;143(2):169-74. doi: 10.1007/BF01816950.
We have studied the localization of neutral sphingomyelinase (N-SMas) in rat liver nuclei. The levels of neutral sphingomyelinase in regenerating liver nuclei were also assessed. We found that rat liver nuclei contain a sphingomyelinase having a pH optima of 7.2 and a kDa of 92. In intact nuclei, neutral sphingomyelinase was associated predominantly with the nuclear envelope. In regenerating/proliferating rat liver (during DNA synthesis), neutral sphingomyelinase was translocated from the nuclear envelope to the nuclear matrix. The levels of sphingomyelin in whole nuclei decreased in reverse proportion to an increase in the levels of neutral sphingomyelinase. By contrast, there was a corresponding increase in the levels of ceramide and sphingosine during cell regeneration/proliferation. Thus, endogenous nuclear neutral sphingomyelinase may play a role in the regulation of sphingomyelin levels and in relevant signal transduction reactions involving cell regeneration/proliferation. The potential significance of ceramide generation may be aimed at programmed cell death to allow the regeneration of liver mediated via target proteins such as, ceramide activated protein kinases/phospholipases or other unknown mechanisms.
我们研究了中性鞘磷脂酶（N-SMas）在大鼠肝细胞核中的定位。还评估了再生肝细胞核中中性鞘磷脂酶的水平。我们发现大鼠肝细胞核含有一种pH最适值为7.2、分子量为92 kDa的鞘磷脂酶。在完整的细胞核中，中性鞘磷脂酶主要与核膜相关。在再生/增殖的大鼠肝脏中（DNA合成期间），中性鞘磷脂酶从核膜转移至核基质。全细胞核中鞘磷脂的水平与中性鞘磷脂酶水平的增加成反比下降。相比之下，在细胞再生/增殖过程中，神经酰胺和鞘氨醇的水平相应增加。因此，内源性核中性鞘磷脂酶可能在鞘磷脂水平的调节以及涉及细胞再生/增殖的相关信号转导反应中发挥作用。神经酰胺生成的潜在意义可能旨在通过诸如神经酰胺激活的蛋白激酶/磷脂酶等靶蛋白或其他未知机制介导的程序性细胞死亡，从而实现肝脏的再生。
