Laboratories of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Institute of Life Science and Technology, Pusan National University, Busan 609-735, Republic of Korea.
Acta Pharmacol Sin. 2009 Oct;30(10):1454-61. doi: 10.1038/aps.2009.136. Epub 2009 Sep 14.
To understand the contribution of sphingolipid metabolism and its metabolites to development and aging.
A systemic analysis on the changes in activity of sphingolipid metabolic enzymes in kidney, liver and brain tissues during development and aging was conducted. The study was conducted using tissues from 1-day-old to 720-day-old rats.
Catabolic enzyme activities as well as the level of sphingomyelinase (SMase) and ceramidase (CDase) were higher than that of anabolic enzyme activities, sphingomyelin synthase and ceramide synthase. This suggested an accumulation of ceramide and sphingosine during development and aging. The liver showed the highest neutral-SMase activity among the tested enzymes while the kidney and brain exhibited higher neutral-SMase and ceramidase activities, indicating a high production of ceramide in liver and ceramide/sphingosine in the kidney and brain. The activities of sphingolipid metabolic enzymes were significantly elevated in all tested tissues during development and aging, although the onset of significant increase in activity varied on the tissue and enzyme type. During aging, 18 out of 21 enzyme activities were further increased on day 720 compared to day 180.
Differential increases in sphingolipid metabolic enzyme activities suggest that sphingolipids including ceramide and sphingosine might play important and dynamic roles in proliferation, differentiation and apoptosis during development and aging.
了解神经酰胺代谢及其代谢产物在发育和衰老中的作用。
系统分析了肾脏、肝脏和脑组织中神经鞘脂代谢酶活性在发育和衰老过程中的变化。该研究使用了 1 天至 720 天龄大鼠的组织。
分解代谢酶的活性以及神经鞘磷脂酶(SMase)和神经酰胺酶(CDase)的水平高于合成代谢酶的活性,即神经鞘磷脂合成酶和神经酰胺合成酶。这表明在发育和衰老过程中神经酰胺和神经鞘氨醇不断积累。肝脏中中性-SMase 的活性最高,而肾脏和大脑中的中性-SMase 和神经酰胺酶活性较高,表明肝脏中神经酰胺的产生较高,而肾脏和大脑中神经酰胺/神经鞘氨醇的产生较高。在发育和衰老过程中,所有测试的组织中神经鞘脂代谢酶的活性均显著升高,尽管活性显著增加的起始时间因组织和酶的类型而异。在衰老过程中,与 180 天相比,21 种酶活性中有 18 种在 720 天时进一步增加。
神经鞘脂代谢酶活性的差异增加表明,神经酰胺包括神经酰胺和神经鞘氨醇,在发育和衰老过程中的增殖、分化和细胞凋亡中可能发挥重要和动态的作用。