title: Chemical and biological insights into uranium-induced apoptosis of rat hepatic cell line.
abstract: Uranium release into the environment is a threat to human health, and the mechanisms of cytotoxicity caused by uranium are not well-understood. To improve our understanding in this respect, we herein evaluated the effects of uranium exposure on normal rat hepatic BRL cells. As revealed by scanning electron microscopy and transmission electron microscope analysis, uranyl nitrate was found to be transformed into uranyl phosphate particles in the medium and taken up by BRL cells in an endocytotic uptake manner, which presumably initiates apoptosis of the cell, although soluble uranyl ion may also be toxic. The apoptosis of BRL cells upon uranium exposure was also confirmed by both the acridine orange and ethidium bromide double staining assay and the Annexin V/propidium iodide double staining assay. Further studies revealed that uranium induced the loss of mitochondrial membrane potential in a dose-dependent manner. Moreover, the uranium-induced apoptosis was found to be associated with the activation of caspase-3, caspase-8 and caspase-9, indicating both a mitochondria-dependent signaling pathway and a death receptor pathway by a crosstalk. This study provides new chemical and biological insights into the mechanism of uranium toxicity toward hepatic cells, which will help seek approaches for biological remediation of uranium.
authors: Key Laboratory of Tumor Cellular and Molecular Pathology, University of South China, College of Hunan Province, Hengyang, 421001, China.
authors: Fang
authors: F
authors: Liu
authors: Ke-Jie
authors: KJ
authors: Du
authors: Zhen
authors: Z
authors: Fang
authors: Yong
authors: Y
authors: You
authors: Ge-Bo
authors: GB
authors: Wen
authors: Ying-Wu
authors: YW
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000528:radiation effects; D008099:Liver / Q000166:cytology*; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D008928:Mitochondria / Q000528:radiation effects; D051381:Rats; D053218:Receptors, Death Domain; D014501:Uranium / Q000633:toxicity*
chemical_list: D053218:Receptors, Death Domain; D014501:Uranium; D020169:Caspases
references: Nat Chem. 2011 Jul 24;3(9):697-703
references: 21860458
references: Toxicol Sci. 2007 Aug;98(2):479-87
references: 17522072
references: Chem Rev. 2003 Nov;103(11):4207-82
references: 14611263
references: Biofizika. 2012 Sep-Oct;57(5):789-95
references: 23136770
references: Lancet. 2001 Jan 27;357(9252):244-6
references: 11214120
references: Biol Trace Elem Res. 2001 Winter;84(1-3):139-54
references: 11817685
references: ScientificWorldJournal. 2002 Mar 15;2:707-29
references: 12805996
references: FEBS Lett. 2008 Dec 10;582(29):4066-76
references: 19022252
references: J Inorg Biochem. 2009 Dec;103(12):1609-16
references: 19800129
references: Toxicology. 2009 Jul 28;262(1):73-9
references: 19460415
references: Arch Toxicol. 2009 Jun;83(6):595-600
references: 19096828
references: Biochemistry. 2007 Feb 27;46(8):2215-26
references: 17266333
references: Int J Cancer. 2006 Dec 15;119(12):2948-57
references: 17036330
references: Spectrochim Acta A Mol Biomol Spectrosc. 2014 Jan 24;118:130-7
references: 24051281
references: J Fluoresc. 2010 Mar;20(2):581-90
references: 20066480
references: Oncogene. 2008 Oct 20;27(48):6194-206
references: 18931687
references: BMC Biotechnol. 2005 May 10;5:12
references: 15885144
references: Radiat Environ Biophys. 2014 May;53(2):321-33
references: 24604722
references: J Mol Model. 2012 Mar;18(3):1009-13
references: 21656240
references: Chem Res Toxicol. 2006 Dec;19(12):1637-42
references: 17173377
references: Environ Health Perspect. 2006 Jan;114(1):85-91
references: 16393663
references: Compr Physiol. 2013 Apr;3(2):977-1010
references: 23720337
references: Biochim Biophys Acta. 2011 Apr;1813(4):558-63
references: 21295084
references: J Toxicol Environ Health B Crit Rev. 2004 Jul-Aug;7(4):297-317
references: 15205046
references: Toxicol Lett. 1999 Feb 22;104(3):249-56
references: 10079060
references: Reprod Toxicol. 2011 May;31(4):470-6
references: 21262344
references: Spectrochim Acta A Mol Biomol Spectrosc. 2013 Jun;110:419-24
references: 23583878
references: J Inorg Biochem. 2011 Feb;105(2):142-8
references: 21194611
references: Environ Health Perspect. 2002 Apr;110(4):337-42
references: 11940450
references: J Biol Inorg Chem. 2008 Jun;13(5):655-62
references: 18273650
references: Chem Res Toxicol. 2004 Mar;17(3):446-52
references: 15025516
references: Lancet. 2002 Dec;360 Suppl:s31-2
references: 12504494
references: Toxicology. 2002 Sep 30;179(1-2):105-14
references: 12204547