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Lysyl Oxidase, A Critical Intra- and Extra-Cellular Target in the Lung for Cigarette Smoke Pathogenesis
Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA
Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, 510089, China
* Author to whom correspondence should be addressed.
Received: 23 November 2010; in revised form: 22 December 2010 / Accepted: 12 January 2011 / Published: 19 January 2011
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.
Keywords: cigarette smoke (CS); CS condensate (CSC); 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); cadmium (Cd); lysyl oxidase (LO); emphysema; carcinogenesis
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Cite This Article
MDPI and ACS Style
Li, W.; Zhou, J.; Chen, L.; Luo, Z.; Zhao, Y. Lysyl Oxidase, A Critical Intra- and Extra-Cellular Target in the Lung for Cigarette Smoke Pathogenesis. Int. J. Environ. Res. Public Health 2011, 8, 161-184.
Li W, Zhou J, Chen L, Luo Z, Zhao Y. Lysyl Oxidase, A Critical Intra- and Extra-Cellular Target in the Lung for Cigarette Smoke Pathogenesis. International Journal of Environmental Research and Public Health. 2011; 8(1):161-184.
Li, Wande; Zhou, Jing; Chen, Lijun; Luo, Zhijun; Zhao, Yinzhi. 2011. "Lysyl Oxidase, A Critical Intra- and Extra-Cellular Target in the Lung for Cigarette Smoke Pathogenesis." Int. J. Environ. Res. Public Health 8, no. 1: 161-184.