Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells.
BACKGROUND
Increasing environmental and occupational exposures to nanoparticles (NPs) warrant deeper insight into the toxicological mechanisms induced by these materials. The present study was designed to characterize the cell death induced by carbon black (CB) and titanium dioxide (TiO2) NPs in bronchial epithelial cells (16HBE14o- cell line and primary cells) and to investigate the implicated molecular pathways.


RESULTS
Detailed time course studies revealed that both CB (13 nm) and TiO2(15 nm) NP exposed cells exhibit typical morphological (decreased cell size, membrane blebbing, peripheral chromatin condensation, apoptotic body formation) and biochemical (caspase activation and DNA fragmentation) features of apoptotic cell death. A decrease in mitochondrial membrane potential, activation of Bax and release of cytochrome c from mitochondria were only observed in case of CB NPs whereas lipid peroxidation, lysosomal membrane destabilization and cathepsin B release were observed during the apoptotic process induced by TiO2 NPs. Furthermore, ROS production was observed after exposure to CB and TiO2 but hydrogen peroxide (H2O2) production was only involved in apoptosis induction by CB NPs.


CONCLUSIONS
Both CB and TiO2 NPs induce apoptotic cell death in bronchial epithelial cells. CB NPs induce apoptosis by a ROS dependent mitochondrial pathway whereas TiO2 NPs induce cell death through lysosomal membrane destabilization and lipid peroxidation. Although the final outcome is similar (apoptosis), the molecular pathways activated by NPs differ depending upon the chemical nature of the NPs.
Hussain
Salik
S
Université Paris Diderot - Paris 7, Unit of Functional and Adaptive Biology (BFA) CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics, 75205 Paris, France.
Thomassen
Leen C J
LC
Ferecatu
Ioana
I
Borot
Marie-Caroline
MC
Andreau
Karine
K
Martens
Johan A
JA
Fleury
Jocelyne
J
Baeza-Squiban
Armelle
A
Marano
Francelyne
F
Boland
Sonja
S
D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000473:pathology; D053260:Soot / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D002843:Chromatin; D017382:Reactive Oxygen Species; D053260:Soot; D051028:bcl-2-Associated X Protein; C009495:titanium dioxide; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D014025:Titanium; D020169:Caspases
Part Fibre Toxicol. 2008 Dec 19;5:22
19099552
Front Biosci. 2006 Sep 01;11:3036-48
16720374
J Exp Med. 1995 Aug 1;182(2):367-77
7629499
J Cell Sci. 2000 Feb;113 ( Pt 4):635-41
10652256
Toxicology. 2008 Mar 12;245(1-2):90-100
18243471
IUBMB Life. 2006 Sep;58(9):531-9
17002981
Am J Respir Cell Mol Biol. 2006 Aug;35(2):155-64
16543604
Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41
18073771
Eur Respir J. 2009 Sep;34(3):559-67
19696157
J Clin Invest. 2000 Nov;106(9):1127-37
11067865
Environ Sci Technol. 2008 Jun 15;42(12):4447-53
18605569
J Agric Food Chem. 2000 Apr;48(4):1150-4
10775364
Am J Physiol Lung Cell Mol Physiol. 2006 Oct;291(4):L725-33
16751223
Eur Respir J. 2002 Feb;19(2):257-66
11866006
Cell Death Differ. 2001 Apr;8(4):324-6
11550083
Environ Sci Technol. 2009 Jun 15;43(12):4227-33
19603627
Am J Respir Crit Care Med. 2001 Nov 1;164(9):1665-8
11719307
Pathophysiology. 2000 Sep;7(3):153-163
10996508
Cancer Res. 2004 Jan 1;64(1):27-30
14729603
Int Arch Occup Environ Health. 2001 Jan;74(1):1-8
11196075
Exp Cell Res. 2005 Jul 1;307(1):76-90
15922728
Oncogene. 2008 Oct 27;27(50):6434-51
18955971
Chest. 2003 Mar;123(3 Suppl):345S
12628970
Am J Pathol. 2009 Nov;175(5):2171-83
19815711
Toxicology. 2005 Sep 15;213(1-2):66-73
15970370
Science. 2006 Feb 3;311(5761):622-7
16456071
FEBS Lett. 2001 Dec 14;509(3):405-12
11749964
Environ Sci Technol. 2006 Jul 15;40(14):4346-52
16903269
Small. 2009 Sep;5(18):2067-76
19642089
J Biol Chem. 2005 Feb 18;280(7):5267-73
15611097
Free Radic Biol Med. 2001 Jun 15;30(12):1347-56
11390179
Environ Sci Technol. 2007 Jun 1;41(11):4158-63
17612205
Chemistry. 2009;15(18):4614-21
19291716
Toxicol Sci. 2006 Jul;92(1):126-32
16597657
Mol Cell. 2002 Mar;9(3):459-70
11931755
Res Rep Health Eff Inst. 2004 Dec;(126):1-47; discussion 49-63
15768531
Clin Immunol. 2003 Dec;109(3):250-65
14697739
Nat Rev Mol Cell Biol. 2008 Jan;9(1):47-59
18097445
Free Radic Biol Med. 1997;22(1-2):269-85
8958153
Pharmacol Ther. 2008 Oct;120(1):35-42
18703086
Oncogene. 2004 Apr 12;23(16):2881-90
15077151
J Leukoc Biol. 1990 May;47(5):440-8
2159514
Cancer Res. 2005 Aug 15;65(16):7436-45
16103097
Apoptosis. 2006 Sep;11(9):1545-59
16738803
Acta Biomater. 2007 May;3(3):351-8
17275430
J Free Radic Biol Med. 1986;2(5-6):359-65
3598065
Inhal Toxicol. 2009 Jul;21 Suppl 1:68-73
19558236
Clin Occup Environ Med. 2006;5(4):817-36
17110294
Phys Chem Chem Phys. 2009 Aug 7;11(29):6205-17
19606331
Cell Death Differ. 2002 Dec;9(12):1307-10
12478467
In Vitro. 1980 Feb;16(2):136-46
6767655
J Clin Invest. 2000 Dec;106(11):1311-9
11104784
Am J Respir Cell Mol Biol. 1994 Jan;10(1):38-47
7507342
Small. 2007 Nov;3(11):1941-9
17963284
Langmuir. 2010 Jan 5;26(1):328-35
19697952
Br J Cancer. 1972 Aug;26(4):239-57
4561027
Acta Pathol Microbiol Immunol Scand A. 1984 Sep;92(5):303-9
6507098
Toxicol Sci. 2004 Jul;80(1):34-48
15056807
J Exp Med. 2003 May 19;197(10):1323-34
12756268
Clin Cancer Res. 2005 May 1;11(9):3155-62
15867207
Science. 1998 Aug 28;281(5381):1312-6
9721091
Am J Physiol Gastrointest Liver Physiol. 2007 Jul;293(1):G296-307
17431216
Toxicology. 2009 Jun 16;260(1-3):142-9
19464580
Toxicol Lett. 1998 Dec 28;102-103:355-8
10022278
FEBS Lett. 1998 Mar 27;425(2):266-70
9559663