Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 24 Tamilnadu, India.
Antonie Van Leeuwenhoek. 2011 Mar;99(3):567-77. doi: 10.1007/s10482-010-9526-1. Epub 2010 Nov 3.
A tobacco-specific nitrosamine (TSNA), N-nitrosonornicotine (NNN), is a potent carcinogen present in cigarette smoke, and chronic exposure to it can lead to pulmonary cancer. NNN causes changes in phospholipid metabolism and the mechanism is yet to be elucidated. Exposure of Saccharomyces cerevisiae to 50 μM NNN leads to a substantial decrease in phosphatidylserine (PS) by 63%, phosphatidylcholine (PC) by 42% and phosphatidylethanolamine (PE) by 36% with a concomitant increase in lysophospholipids (LPL) by 25%. The alteration in phospholipid content was dependent on increasing NNN concentration. Reduced phospholipids were accompanied with increased neutral lipid content. Here we report for the first time that NNN exposure, significantly increases phospholipase B (PLB) activity and the preferred substrate is PC, a major phospholipid responsible for a series of metabolic functions. Furthermore, NNN also promotes the alteration of fatty acid (FA) composition; it increases the long chain fatty acid (C18 series) in phospholipids specifically phosphatidylethanolamine (PE) and PS; while on the contrary it increases short chain fatty acids in cardiolipin (CL). NNN mediated degradation of phospholipids is associated with enhanced PLB activity and alteration of phospholipid composition is accompanied with acyl chain remodelling. Understanding the altered phospholipid metabolism produced by NNN exposure is a worthwhile pursuit because it will help to understand the toxicity of tobacco smoke.
一种烟草特异性亚硝胺（TSNA），N-亚硝基降烟碱（NNN），是一种存在于香烟烟雾中的强致癌物质，慢性暴露于 NNN 可导致肺癌。NNN 导致磷脂代谢变化，但其机制尚未阐明。酵母暴露于 50μM 的 NNN 会导致磷脂酰丝氨酸（PS）显著减少 63%，磷脂酰胆碱（PC）减少 42%，磷脂酰乙醇胺（PE）减少 36%，同时溶血磷脂（LPL）增加 25%。磷脂含量的改变依赖于 NNN 浓度的增加。减少的磷脂伴随着中性脂质含量的增加。本文首次报道 NNN 暴露显著增加了磷脂酶 B（PLB）的活性，其优先底物是 PC，PC 是一种主要的磷脂，负责一系列代谢功能。此外，NNN 还促进了脂肪酸（FA）组成的改变；它增加了磷脂，特别是磷脂酰乙醇胺（PE）和磷脂酰丝氨酸（PS）中的长链脂肪酸（C18 系列）；而相反，它增加了心磷脂（CL）中的短链脂肪酸。NNN 介导的磷脂降解与 PLB 活性的增强有关，而磷脂组成的改变伴随着酰基链的重塑。了解 NNN 暴露引起的磷脂代谢变化是值得研究的，因为它有助于理解烟草烟雾的毒性。
