Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic c

[Guest guest]

_Toxicology _

(http://www.sciencedirect.com/science?_ob=JournalURL & _cdi=5175 & _auth=y & _acct=C00\

0050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=a614fbeb7cd441

5dfb9d501a5627e44f)

_Volume 225, Issues 2-3_

(http://www.sciencedirect.com/science?_ob=IssueURL & _tockey=#TOC#5175#2006#997749\

997#628967#FLA# & _auth=y & view=c & _acct=C000050221 & _v

ersion=1 & _urlVersion=0 & _userid=10 & md5=ead5dc94819eb83bc1bf682e9008d1be) , 15

August 2006, Pages 234-241

_doi:10.1016/j.tox.2006.06.006_ (http://dx.doi.org/10.1016/j.tox.2006.06.006)

(http://www.sciencedirect.com/science?_ob=HelpURL & _file=doi.htm & _acct=C000050221\

& _version=1 & _urlVersion=0 & _userid=10 & md5=a143a86ddc585c54adbe80b2046626

c3)

Copyright © 2006 Elsevier Ireland Ltd All rights reserved.

Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and

hypothalamic cell lines

Helene Stockmann-Juvala_a_

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cover\

Date=08/15/2006 & _alid=431629625 & _rdoc=1 & _fmt= & _or

ig=search & _qd=1 & _cdi=5175 & _sort=d & view=c & _acct=C000050221 & _version=1 & _urlVersi

on=0 & _userid=10 & md5=2b83b8878d3e9ed6041aec8956b75938#aff1) ,

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cover\

Date=08/15/200

6 & _alid=431629625 & _rdoc=1 & _fmt= & _orig=search & _qd=1 & _cdi=5175 & _sort=d & view=c & _a

cct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=2b83b8878d3e9ed6041aec8

956b75938#cor1) , (mailto:helene.stockmann-juvala@...) , Jonne Naarala_b_

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cov

erDate=08/15/2006 & _alid=431629625 & _rdoc=1 & _fmt= & _orig=search & _qd=1 & _cdi=5175 & _

sort=d & view=c & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=2b83b88

78d3e9ed6041aec8956b75938#aff2) , Jarkko Loikkanen_c_

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cover\

Date=08/15/2006 & _alid

=431629625 & _rdoc=1 & _fmt= & _orig=search & _qd=1 & _cdi=5175 & _sort=d & view=c & _acct=C00

0050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=2b83b8878d3e9ed6041aec8956b759

38#aff3) , Kirsi Vähäkangas_c_

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cover\

Date=08/15/2006 & _alid=431629625 & _rdoc=1 & _fmt

= & _orig=search & _qd=1 & _cdi=5175 & _sort=d & view=c & _acct=C000050221 & _version=1 & _url

Version=0 & _userid=10 & md5=2b83b8878d3e9ed6041aec8956b75938#aff3) and Kai

Savolainen_d_

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cover\

Date=08/15/2006 & _alid=431629625 & _rdoc=1 & _fmt= & _orig=search & _qd=1 & _

cdi=5175 & _sort=d & view=c & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & m

d5=2b83b8878d3e9ed6041aec8956b75938#aff4)

aUnit of Excellence for Immunotoxicology, Finnish Institute of Occupational

Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland

bDepartment of Environmental Sciences, University of Kuopio, PO Box 1627,

70211 Kuopio, Finland

cDepartment of Pharmacology and Toxicology, University of Kuopio, PO Box

1627, 70211 Kuopio, Finland

dNew Technologies and Risks, Finnish Institute of Occupational Health,

Topeliuksenkatu 41 a A, 00250 Helsinki, Finland

Received 17 April 2006; revised 5 June 2006; accepted 8 June 2006.

Available online 13 June 2006.

Abstract

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium verticilliodes, which

commonly infects corn across the world. Fusarium fungi may also be found in

moisture-damaged buildings. In this study, we investigated the role of

apoptosis in the toxicity of FB1 in four different cell lines. Activation of

caspase-3-like protease, DNA fragmentation and expression of p53 and Bcl-2

family

proteins were studied in mouse GT1-7 hypothalamic, rat C6 glioblastoma, human

U-118MG glioblastoma, and human SH-SY5Y neuroblastoma cells exposed to 0.1–

100 μM FB1 for 0–144 h. Caspase-3-like protease activity increased in all

cell

lines, except SH-SY5Y, at 48–144 h, and internucleosomal DNA fragmentation

occurred in all of the cell lines, pointing to a role for apoptosis in the

toxicity of FB1. However, the expressions of p53 or pro- or antiapoptotic Bcl-2

family proteins (Bax, Bcl-2, Bcl-XL and Mcl-1) were not affected in any of

the cell lines even after prolonged exposure to FB1 at high doses. The results

of this study, together with the results of our previous studies, provide

evidence that FB1 is a potential neurotoxin, but that the toxicity of FB1

varies between different cell lines. The sensitivity of these cell lines

towards

FB1 is as follows: U-118MG > GT1-7 > C6 > SH-SY5Y cells. These results are

consistent with the assumption that cells of glial origin may be more

sensitive towards FB1 than cells of neural origin.

Keywords: Fumonisin B1; Apoptosis; Neurotoxicity; Caspase-3; Bcl-2; p53

(http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6TCN-4K5RBJT-1 & _cover\

Date=08/15/2006 & _alid=431629625 & _rdoc=1 & _fmt= & _orig=search & _qd=1 & _cdi=5175 &

_sort=d & view=c & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=2b83b8

878d3e9ed6041aec8956b75938#bcor1) Corresponding author. Tel.: +358 30

4742146; fax: +358 30 4742208.