title: Profiling of acyl-CoA oxidase-deficient and peroxisome proliferator Wy14,643-treated mouse liver protein by surface-enhanced laser desorption/ionization ProteinChip Biology System.
abstract: Peroxisome proliferators induce hepatic peroxisome proliferation and hepatocellular carcinomas in rodents. These chemicals increase the expression of the peroxisomal beta-oxidation pathway and the cytochrome P-450 4A family, which metabolizes lipids, including fatty acids. Mice lacking fatty acyl-CoA oxidase (AOX-/-), the first enzyme of the peroxisomal beta-oxidation system, exhibit extensive microvesicular steatohepatitis, leading to hepatocellular regeneration and massive peroxisome proliferation. To investigate proteins involved in peroxisome proliferation, we adopted a novel surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology to compare the protein profiles of control (wild-type), AOX-/-, and wild-type mice treated with peroxisome proliferator, Wy-14,643. The results indicated that the protein profiles of AOX-/- mice were similar to the wild-type mice treated with Wy14,643, but significantly different from the nontreated wild-type mice. Using four different ProteinChip Arrays, a total of 40 protein peaks showed more than twofold changes. Among these differentially expressed peaks, a downregulated peak was identified as the major urinary protein in both AOX-/- and Wyl4,643-treated mice by SELDI. The identification of MUP was further confirmed by two-dimensional electrophoresis and liquid chromatography coupled tandem mass spectrometry (LC-MS-MS). This SELDI method offers several technical advantages for detection of differentially expressed proteins, including ease and speed of screening, no need for chromatographic processing, and small sample size.
authors.affiliation: Department of Functional Genomics, Aventis Pharmaceuticals, Inc., Bridgewater, NJ 08807, USA. ruiyin.chu@aventis.com
authors.forename: Ruiyin
authors.initials: R
authors.lastname: Chu
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
authors.forename: Hanjo
authors.initials: H
authors.lastname: Lim
authors.forename: Anjana V
authors.initials: AV
authors.lastname: Yeldandi
authors.forename: Chris
authors.initials: C
authors.lastname: Herring
authors.forename: Laura
authors.initials: L
authors.lastname: Brumfield
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
authors.forename: Matthew
authors.initials: M
authors.lastname: Davison
mesh_terms: D042962:Acyl-CoA Oxidase; D000818:Animals; D002455:Cell Division; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010088:Oxidoreductases / Q000235:genetics* / Q000502:physiology; D010455:Peptides / Q000737:chemistry; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D040081:Protein Array Analysis / Q000379:methods*; D011506:Proteins / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D011743:Pyrimidines / Q000494:pharmacology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D010455:Peptides; D020025:Peroxisome Proliferators; D011506:Proteins; D020543:Proteome; D011743:Pyrimidines; C035737:major urinary proteins; C006253:pirinixic acid; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase