Document Detail

Endothelial nitric oxide synthase uncoupling as a key mediator for melanocyte malignant transformation associated with sustained stress condition.
MedLine Citation:
PMID:  21362470     Owner:  NLM     Status:  Publisher    
Melanoma cell lines and cells corresponding to pre-malignant melanocytes were established by our group after submitting a non-tumorigenic murine melanocyte lineage, melan-a, to sequential cycles of anchorage blockade. Previous results showed that in melan-a cells superoxide level increases after such procedure. Superoxide production during melanocyte de-adhesion was inhibited by L-sepiapterin, precursor of eNOS cofactor BH4, and increased with inhibitor of BH4 synthesis, DAHP, hence indicating a partial uncoupling state of eNOS. The eNOS uncoupling seems to be maintained in cells derived from melan-a, since they present decreased nitric oxide and increased superoxide levels. The inhibition of superoxide production in Tm5 melanoma cells with L-sepiapterin reinforces their eNOS uncoupled state. The maintenance of oxidative stress seems to be important in melanoma apoptosis resistance since Mn(III)TBAP, a superoxide scavenger, or L-sepiapterin render Tm5 cells more sensitive to anoikis and chemotherapy. More importantly, eNOS uncoupling seems to exert a pivoltal role in melanocyte malignant transformation induced by sustained anchorage impediment, since no malignant transformation was observed when L-NAME-treated melanocytes were submitted to sequential cycles of de-adhesion. Our results show that uncoupled eNOS contribute to superoxide production during melanocyte anchorage impediment, contributing to anoikis resistance and malignant transformation.
Fabiana H M Melo; Fernanda Molognoni; Alice S Morais; Mariana Toricelli; Margareth G Mouro; Elisa M S Higa; José D Lopes; Miriam G Jasiulionis
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-26
Journal Detail:
Title:  Free radical biology & medicine     Volume:  -     ISSN:  1873-4596     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-3-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010. Published by Elsevier Inc.
Disciplina de Imunologia, Universidade Federal de São Paulo, UNIFESP.
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