Identification of liver proteins and their roles associated with carbon tetrachloride-induced hepatotoxicity.
Carbon tetrachloride (CCl(4)) is a common hepatotoxin used in experimental models to elicit liver injury. To identify the proteins involved in CCl(4)-induced hepatotoxicity, two-dimensional gel electrophoresis was employed followed by mass spectrometry - mass spectrometry (MS/MS) to study the differentially expressed proteins during CCl(4) exposure in the Fischer 344 rat liver proteome for 5 weeks. Ten spots with notable changes between the Control and CCl(4) groups were successfully identified. Among them, four proteins with significant up-regulation, namely calcium-binding protein 1, protein disulfide isomerase, mitochondrial aldehyde dehydrogenase precursor, and, glutathione-S-transferase mu1 and six proteins with significant down-regulation, namely catechol-O-methyltransferase, hemoglobin-alpha-2-chain, hemopexin precursor, methionine sulfoxide reductase A, catalase and carbonic anhydrase 3, were identified. The data indicates that CCl(4) causes hepatotoxicity by depleting oxygen radical scavengers in the hepatocytes. In this rat model, we profiled hepatic proteome alterations in response to CCl(4) intoxication. The findings should facilitate understanding of the mechanism of CCl(4)-induced liver injury.
School of Biological Sciences, The University of Hong Kong, HKSAR, China.
Leo Lap Yan
LL
Wong
Sheung Tat
ST
Fan
Kwan
K
Man
Wai-Hung
WH
Sit
Ping Ping
PP
Jiang
Irene Wing-Yan
IW
Jor
Carol Yee-Ki
CY
Lee
Wai Lim
WL
Ling
Kin Tung
KT
Tam
Jennifer Man-Fan
JM
Wan
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000302:isolation & purification* / Q000502:physiology; D020543:Proteome / Q000302:isolation & purification / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
D000596:Amino Acids; D011506:Proteins; D020543:Proteome; D002251:Carbon Tetrachloride