title: Lysyl oxidase, a critical intra- and extra-cellular target in the lung for cigarette smoke pathogenesis.
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.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. wandeli@bu.edu
authors.forename: Wande
authors.initials: W
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Lijun
authors.initials: L
authors.lastname: Chen
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Luo
authors.forename: Yinzhi
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002104:Cadmium / Q000378:metabolism / Q000633:toxicity; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity; D015536:Down-Regulation; D004646:Emphysema / Q000201:enzymology / Q000209:etiology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis* / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000209:etiology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000378:metabolism* / Q000503:physiopathology; D014026:Nicotiana / Q000737:chemistry* / Q000633:toxicity*
chemical_list: D002273:Carcinogens; C000715470:MAS1 protein, human; D009602:Nitrosamines; D000090063:Proto-Oncogene Mas; D012906:Smoke; D002104:Cadmium; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D008249:Protein-Lysine 6-Oxidase