Cigarette smoking induces overexpression of a fat-depleting gene AZGP1 in the human.
نویسندگان
چکیده
BACKGROUND Smokers weigh less and have less body fat than nonsmokers. Increased body fat and weight gain are observed following smoking cessation. To assess a possible molecular mechanism underlying the inverse association between smoking and body weight, we hypothesized that smoking may induce the expression of a fat-depleting gene in the airway epithelium, the cell population that takes the brunt of the stress of cigarette smoke. METHODS To assess whether smoking up-regulates expression in the airway epithelium of genes associated with weight loss, microarray analysis was used to evaluate genes associated with fat depletion in large airway epithelial samples obtained by fiberoptic bronchoscopy from healthy smokers and healthy nonsmokers. As a candidate gene we further evaluated the expression of alpha(2)-zinc-glycoprotein 1 (AZGP1), a soluble protein that stimulates lipolysis, induces a reduction in body fat in mice, is associated with the cachexia related to cancer, and is known to be expressed in secretory cells of lung epithelium. AZGP1 protein expression was assessed by Western analysis and localization in the large airway epithelium by immunohistochemistry. RESULTS Both microarray and TaqMan analysis demonstrated that AZGP1 messenger RNA levels were higher in the large airway epithelium of healthy smokers compared to healthy nonsmokers (p < 0.05, all comparisons). Western analysis of airway biopsy specimens from smokers compared with those from nonsmokers demonstrated up-regulation of AZGP1 at the protein level, and immunohistochemical analysis demonstrated up-regulation of AZGP1 in secretory as well as neuroendocrine cells of smokers. CONCLUSIONS In the context that AZGP1 is involved in lipolysis and fat loss, its overexpression in the airway epithelium of chronic smokers may represent one mechanism for the weight difference in smokers vs nonsmokers.
منابع مشابه
The Effect of Cigarette Smoking on Human Sperm Creatine Kinase Activity: As An ATP Buffering System in Sperm
متن کامل
Synergistic Effects of NDRG2 Overexpression and Radiotherapy on Cell Death of Human Prostate LNCaP Cells
Background: Radiation therapy is among the most conventional cancer therapeutic modalities with effective local tumor control. However, due to the development of radio-resistance, tumor recurrence and metastasis often occur following radiation therapy. In recent years, combination of radiotherapy and gene therapy has been suggested to overcome this problem. The aim of the current study was to e...
متن کاملHPV18 E7 induces the over-transcription of eIF4E gene in cervical cancer
Objective(s):Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in cervical cancer (CC). However, the molecular mechanisms are unclear. This study aimed to investigate the molecular mechanism of eIF4E gene overexpression in CC. Materials andMethods:The human papillomavirus (HPV) type 18 E7 and eIF4E mRNAs were measured following knock down or overexpression of E7 gene by RT-P...
متن کاملAlpha-2-Glycoprotein 1(AZGP1) Regulates Biological Behaviors of LoVo Cells by Down-Regulating mTOR Signaling Pathway and Endogenous Fatty Acid Synthesis
AZGP1 is a multifaceted protein associated with lipid mobilization, a process that is regulated by FASN and other metabolic pathways such as mTOR signaling. The active mTOR signaling pathway has been found to be involved in a variety of tumors. However, it remains unclear whether it is involved in the regulation of AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human colorec...
متن کاملThe Impact of Opium Dependence and Cigarette Smoking on Human Semen Parameters
Introduction: To examine the effects of opium dependence and cigarette smoking on semen quality and sperm parameters, the semen quality of men who abuse opiates and/or smoke cigarettes was investigated in a retrospective study. Methods: Male partners of 1325 infertile couples attending the infertility clinic for intrauterine insemination (IUI) procedure were divided into non-smoking non-op...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Chest
دوره 135 5 شماره
صفحات -
تاریخ انتشار 2009