Kammerl, I.E. ; Caniard, A. ; Merl-Pham, J. ; Ben-Nissan, G.* ; Mayr, C.H. ; Mossina, A. ; Geerlof, A. ; Eickelberg, O. ; Hauck, S.M. ; Sharon, M.* ; Meiners, S.
     
 
    
        
Dissecting the molecular effects of cigarette smoke on proteasome function.
    
    
        
    
    
        
        J. Proteomics 193, 1-9 (2019)
    
    
    
		
		
			
				Proteasome dysfunction is emerging as a novel pathomechanism for the development of chronic obstructive pulmonary disease (COPD), a major leading cause of death in the world. Cigarette smoke, one of the main risk factors for COPD, impairs proteasome function in vitro and in vivo. In the present study, we dissected the molecular changes induced by cigarette smoke on the proteasome in lung epithelial cells and mouse lungs. 26S proteasome pull-down, MS interactome, and stoichiometry analyses indicated that 26S proteasome complexes become instable in cigarette smoke-treated lung epithelial cells as well as in lungs of mice after three day smoke exposure. The interactome of the 26S was clearly altered in mouse lungs upon smoke exposure but not in cells after 24 h of smoke exposure. Using native MS analysis of purified 20S proteasomes, we observed some destabilization of 20S complexes purified from cigarette smoke-exposed cells in the absence of any dominant and inhibitory modification of proteasomal proteins. Taken together, our results suggest that cigarette smoke induces minor but detectable changes in the stability of 20S and 26S proteasome complexes which might contribute to imbalanced proteostasis in a chronic setting as observed in chronic lung diseases associated with cigarette smoking.
			
			
				
			
		 
		
			
				
					
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        Publikationstyp
        Artikel: Journalartikel
    
 
    
        Dokumenttyp
        Wissenschaftlicher Artikel
    
 
    
        Typ der Hochschulschrift
        
    
 
    
        Herausgeber
        
    
    
        Schlagwörter
        26s Proteasome Interactome ; Cigarette Smoke ; Native Ms Analysis ; Proteasome; 26s Proteasome; 20s Proteasome; S Proteasomes; Protein; Degradation; Complexes; Antigen; Phosphorylation; Immunoproteasome; Identification
    
 
    
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        Sprache
        englisch
    
 
    
        Veröffentlichungsjahr
        2019
    
 
    
        Prepublished im Jahr 
        2018
    
 
    
        HGF-Berichtsjahr
        2018
    
 
    
    
        ISSN (print) / ISBN
        1874-3919
    
 
    
        e-ISSN
        1876-7737
    
 
    
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	    Band: 193,  
	    Heft: ,  
	    Seiten: 1-9 
	    Artikelnummer: ,  
	    Supplement: ,  
	
    
 
  
        
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            Verlag
            Elsevier
        
 
        
            Verlagsort
            Po Box 211, 1000 Ae Amsterdam, Netherlands
        
 
	
        
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            0000-00-00
        
 
        
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        Begutachtungsstatus
        Peer reviewed
    
 
     
    
        POF Topic(s)
        30202 - Environmental Health
80000 - German Center for Lung Research
30203 - Molecular Targets and Therapies
    
 
    
        Forschungsfeld(er)
        Lung Research
Enabling and Novel Technologies
    
 
    
        PSP-Element(e)
        G-501600-004
G-501810-005
G-505700-001
G-503000-001
G-501800-810
A-630700-001
    
 
    
        Förderungen
        
    
 
    
        Copyright
        
    
 	
    
    
    
    
    
        Erfassungsdatum
        2019-01-08