Vijayaraj Panneerselvam, Sivaprakasam Chinnarasu, Varthini Lakshmanaperumal Vishnu, Sarkar Mary, Nachiappan Vasanthi
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
Biochemistry Department, Indian Institute of Science, Bangalore 560012, India.
Toxicol In Vitro. 2014 Sep;28(6):1097-105. doi: 10.1016/j.tiv.2014.05.001. Epub 2014 May 15.
Tobacco-specific nitrosamines (TSNA) have implications in the pathogenesis of various lung diseases and conditions are prevalent even in non-smokers. N-nitrosonornicotine (NNN) and 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent pulmonary carcinogens present in tobacco product and are mainly responsible for lung cancer. TSNA reacts with pulmonary surfactants, and alters the surfactant phospholipid. The present study was undertaken to investigate the in vitro exposure of rat lung tissue slices to NNK or NNN and to monitor the phospholipid alteration by [(32)P]orthophosphate labeling. Phospholipid content decreased significantly in the presence of either NNK or NNN with concentration and time dependent manner. Phosphatidylcholine (PC) is the main phospholipid of lung and significant reduction was observed in PC ∼61%, followed by phosphatidylglycerol (PG) with 100μM of NNK, whereas NNN treated tissues showed a reduction in phosphatidylserine (PS) ∼60% and PC at 250μM concentration. The phospholipase A2 assays and expression studies reveal that both compounds enhanced phospholipid hydrolysis, thereby reducing the phospholipid content. Collectively, our data demonstrated that both NNK and NNN significantly influenced the surfactant phospholipid level by enhanced phospholipase A2 activity.
烟草特异性亚硝胺（TSNA）与多种肺部疾病的发病机制有关，即使在非吸烟者中也普遍存在。N-亚硝基降烟碱（NNN）和4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）是烟草制品中存在的强效肺致癌物，主要导致肺癌。TSNA与肺表面活性剂发生反应，并改变表面活性剂磷脂。本研究旨在调查大鼠肺组织切片在体外暴露于NNK或NNN的情况，并通过[（32）P]正磷酸盐标记监测磷脂的变化。在NNK或NNN存在下，磷脂含量以浓度和时间依赖性方式显著降低。磷脂酰胆碱（PC）是肺的主要磷脂，在NNK浓度为100μM时，PC显著减少约61%，其次是磷脂酰甘油（PG）；而在250μM浓度的NNN处理的组织中，磷脂酰丝氨酸（PS）减少约60%，PC也减少。磷脂酶A2测定和表达研究表明，这两种化合物均增强了磷脂水解，从而降低了磷脂含量。总体而言，我们的数据表明，NNK和NNN均通过增强磷脂酶A2活性显著影响表面活性剂磷脂水平。
