Abstract
Cigarette smoke (CS), a complex chemical mixture, contains more than 4,800 different compounds, including oxidants, heavy metals, and carcinogens, that individually or in combination initiate or promote pathogenesis in the lung accounting for 82% of chronic obstructive pulmonary disease (COPD) deaths and 87% of lung cancer deaths. Lysyl oxidase (LO), a Cu-dependent enzyme, oxidizes peptidyl lysine residues in collagen, elastin and histone H1, essential for stabilization of the extracellular matrix and cell nucleus. Considerable evidences have shown that LO is a tumor suppressor as exemplified by inhibiting transforming activity of ras, a proto oncogene. CS condensate (CSC), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and cadmium (Cd), major components of CS, down-regulate LO expression at such multiple levels as mRNA, protein and catalytic activity in lung cells in vitro and in vivo indicating LO as a critical intra- and extracellular target for CS pathogenesis in the lung. In view of multiple biological functions and regulation characteristics of the LO gene, molecular mechanisms for CS damage to lung LO and its role in emphysema and cancer pathogenesis are discussed in this review.
Highlights
IntroductionCigarette smoke (CS) is one of the most important risk factors for human disease, accounting for 82% of chronic obstructive pulmonary disease (COPD) deaths and 87% of lung cancer deaths [1,2,3,4]
Cigarette smoke (CS) is one of the most important risk factors for human disease, accounting for 82% of chronic obstructive pulmonary disease (COPD) deaths and 87% of lung cancer deaths [1,2,3,4].Approximately 23% of the US adults currently smoke because of addiction to nicotine, an important component of CS
Additional lysyl oxidase (LO)-like cDNA species encode a variety of LO-like proteins, including LOXL, LOXL2, LOXL3 and LOXL4 [56] which have the homology at the C-terminal domain in comparison to the mature LO
Summary
Cigarette smoke (CS) is one of the most important risk factors for human disease, accounting for 82% of chronic obstructive pulmonary disease (COPD) deaths and 87% of lung cancer deaths [1,2,3,4]. CS-activated macrophages and neutrophils release elastase that proteolyses elastin fibers contributing to lung injury [8,9]. This hypothesis cannot explain all aspects of the emphysema pathology. Cessation of smoking sharply declines pulmonary carcinogenesis in ex-smokers after approximately five years since quitting in comparison to continuous smokers [12], indicating CS as an important risk factor for lung cancers. It is important and necessary to deeply investigate molecular mechanisms and preventing and therapeutic strategies for CS-induced lung diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
