Document Detail


Heme oxygenase-1 attenuates the cisplatin-induced apoptosis of auditory cells via down-regulation of reactive oxygen species generation.
MedLine Citation:
PMID:  16678019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heme oxygenase-1 (HO-1), the rate-limiting enzyme of heme catabolism, is known to modulate various cellular functions, including cytokine production, cell proliferation, and apoptosis, in stress-related conditions. However, the role of HO-1 in the auditory system remains elusive. Herein, we demonstrate that pharmacologic induction of HO-1 along with catalytic activation significantly suppressed apoptosis of HEI-OC1 cells induced by cisplatin. Studies of ectopic expression of pcDNA3-HO-1 and siRNA of HO-1 further revealed the protective role of HO-1 against cisplatin in HEI-OC1 cells. Among the catabolic metabolites of HO-1, both carbon monoxide (CO) and bilirubin were directly involved in the protective role of HO-1 against cisplatin through inhibition of reactive oxygen species generation. Furthermore, pharmacological induction of HO-1 completely prevented the destruction of outer hair cell arrays by cisplatin through a CO-dependent mechanism in organotrophic culture of the rat primary organ of Corti explants. These results suggest that HO-1 may serve as a safeguard of auditory sensory hair cells against a variety of challenges of oxidative stress, including noise trauma, presbycusis, and ototoxic drugs, respectively.
Authors:
Hyung-Jin Kim; Hong-Seob So; Jeong-Han Lee; Jae-Hyung Lee; Channy Park; Sung-Yeol Park; Yun-Ha Kim; Myung-Ja Youn; Se-Jin Kim; Sang-Young Chung; Kang-Min Lee; Raekil Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-08
Journal Detail:
Title:  Free radical biology & medicine     Volume:  40     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-08     Completed Date:  2006-08-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1810-9     Citation Subset:  IM    
Affiliation:
Vestibulocochlear Research Center (VCRC) and Department of Microbiology, Wonkwang University School of Medicine, 344-2 Shinyong-dong Iksan, Jeonbuk 570-749, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Cell Line
Cisplatin / pharmacology*
Down-Regulation
Hair Cells, Auditory / drug effects*,  metabolism,  pathology
Heme Oxygenase-1 / metabolism*
Hemin / pharmacology
Mice
Protoporphyrins / pharmacology
Reactive Oxygen Species / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transfection
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Protoporphyrins; 0/Reactive Oxygen Species; 14325-03-2/cobaltiprotoporphyrin; 15663-27-1/Cisplatin; 16009-13-5/Hemin; EC 1.14.99.3/Heme Oxygenase-1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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