Modeling cellular metabolomic effects of oxidative stress impacts from hydrogen peroxide and cigarette smoke on human lung epithelial cells

2019 ◽  
Vol 13 (3) ◽  
pp. 036014 ◽  
Author(s):  
Mei S Yamaguchi ◽  
Mitchell M McCartney ◽  
Alexandria K Falcon ◽  
Angela L Linderholm ◽  
Susan E Ebeler ◽  
...  
2010 ◽  
Vol 24 (1) ◽  
pp. 310-318 ◽  
Author(s):  
William E. Wixted ◽  
Chris Kitson ◽  
Jayne C. Colebrook ◽  
Emma J. Roberts ◽  
Steven M. Fox ◽  
...  

2013 ◽  
Vol 24 (6) ◽  
pp. 858-869 ◽  
Author(s):  
Sudjit Luanpitpong ◽  
Pithi Chanvorachote ◽  
Christian Stehlik ◽  
William Tse ◽  
Patrick S. Callery ◽  
...  

Hydrogen peroxide is a key mediator of oxidative stress known to be important in various cellular processes, including apoptosis. B-cell lymphoma-2 (Bcl-2) is an oxidative stress–responsive protein and a key regulator of apoptosis; however, the underlying mechanisms of oxidative regulation of Bcl-2 are not well understood. The present study investigates the direct effect of H2O2on Bcl-2 cysteine oxidation as a potential mechanism of apoptosis regulation. Exposure of human lung epithelial cells to H2O2induces apoptosis concomitant with cysteine oxidation and down-regulation of Bcl-2. Inhibition of Bcl-2 oxidation by antioxidants or by site-directed mutagenesis of Bcl-2 at Cys-158 and Cys-229 abrogates the effects of H2O2on Bcl-2 and apoptosis. Immunoprecipitation and confocal microscopic studies show that Bcl-2 interacts with mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2 [ERK1/2]) to suppress apoptosis and that this interaction is modulated by cysteine oxidation of Bcl-2. The H2O2-induced Bcl-2 cysteine oxidation interferes with Bcl-2 and ERK1/2 interaction. Mutation of the cysteine residues inhibits the disruption of Bcl-2–ERK complex, as well as the induction of apoptosis by H2O2. Taken together, these results demonstrate the critical role of Bcl-2 cysteine oxidation in the regulation of apoptosis through ERK signaling. This new finding reveals crucial redox regulatory mechanisms that control the antiapoptotic function of Bcl-2.


2010 ◽  
Vol 242 (1) ◽  
pp. 100-108 ◽  
Author(s):  
Ralph Feltens ◽  
Iljana Mögel ◽  
Carmen Röder-Stolinski ◽  
Jan-Christoph Simon ◽  
Gunda Herberth ◽  
...  

2009 ◽  
Vol 22 (3) ◽  
pp. 492-503 ◽  
Author(s):  
Suryanarayana V. Vulimiri ◽  
Manoj Misra ◽  
Jonathan T. Hamm ◽  
Matthew Mitchell ◽  
Alvin Berger

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