In vitro exposure of tobacco specific nitrosamines decreases the rat lung phospholipids by enhanced phospholipase A2 activity.
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.
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
Panneerselvam
P
Vijayaraj
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
Chinnarasu
C
Sivaprakasam
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
Lakshmanaperumal Vishnu
LV
Varthini
Biochemistry Department, Indian Institute of Science, Bangalore 560012, India.
Mary
M
Sarkar
Biomembrane Lab, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India. Electronic address: vasanthibch@gmail.com.
Vasanthi
V
Nachiappan
D000818:Animals; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D054467:Phospholipases A2 / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D017208:Rats, Wistar
D009602:Nitrosamines; D010743:Phospholipids; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D054467:Phospholipases A2; C008655:N'-nitrosonornicotine
Dipalmitoylphosphatidylcholine; Phospholipase A(2); Phospholipids; Pulmonary surfactant; Tobacco specific nitrosamines