Enhanced phospholipase B activity and alteration of phospholipids and neutral lipids in Saccharomyces cerevisiae exposed to N-nitrosonornicotine

Abstract

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.

Exposure to benzene metabolites causes oxidative damage in Saccharomyces cerevisiae

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Glutathione peroxidase3 of Saccharomyces cerevisiae protects phospholipids during cadmium-induced oxidative stress

“…Yeast cells respond to environmental toxicant by altering the composition of cellular phospholipids (Vijayaraj et al 2010). The main aim of this study is to elucidate the role of gpx3 in protecting phospholipids against Cd-induced oxidative stress in Saccharomyces cerevisiae.…”

Tobacco Smoke-Induced Alterations in Hepatic Lipid Profiles Demonstrated by Imaging Mass Spectrometry

“…Of note is that tobacco-specific nitrosamines decrease lung phospholipids (phosphatidylcholine, phosphatidylglycerol, and phosphatidylserine) by enhancing phospholipase A2 activity [70]. Moreover, nitrosamineinduced reductions in phospholipids can be accompanied by increases in neutral lipids [71]. Therefore, tobacco-specific nitrosamines in CS may mediate their adverse effects on insulin/IGF signaling in liver by inhibiting phospholipid synthesis or maintenance via increased activation of Phospholipase B. Persistence or worsening of lipid ion profile shifts over time, despite CS withdrawal, suggests that CS- data acquired in the negative-ionization mode.…”