title: Proteomic alterations in mouse kidney induced by andrographolide sodium bisulfite.
abstract: OBJECTIVE
  To identify the key proteins involved in the nephrotoxicity induced by andrographolide sodium bisulfite (ASB).
  
  
  METHODS
  Male ICR mice were intravenously administrated with ASB (1000 or 150 mg·kg⁻¹·d⁻¹) for 7 d. The level of malondialdehyde (MDA) and the specific activity of superoxide dismutase (SOD) in kidneys were measured. The renal homogenates were separated by two-dimensional electrophoresis, and the differential protein spots were identified using a matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF)/TOF mass spectrometry.
  
  
  RESULTS
  The high dose (1000 mg/kg) of ASB significantly increased the MDA content, but decreased the SOD activity as compared to the control mice. The proteomic analysis revealed that 6 proteins were differentially expressed in the high-dose group. Two stress-responsive proteins, ie heat shock cognate 71 kDa protein (HSC70) and peroxiredoxin-6 (PRDX6), were regulated at the expression level. The remaining 4 proteins involving in cellular energy metabolism, including isoforms of methylmalonyl-coenzyme A mutase (MUT), nucleoside diphosphate-linked moiety X motif 19 (Nudix motif19), mitochondrial NADH dehydrogenase 1 alpha subcomplex subunit 10 (NDUFA10) and nucleoside diphosphate kinase B (NDK B), were modified at the post-translational levels.
  
  
  CONCLUSIONS
  Our findings suggest that the mitochondrion is the primary target of ASB and that ASB-induced nephrotoxicity results from oxidative stress mediated by superoxide produced by complex I.
authors.affiliation: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, China. luhong03@hotmail.com
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Xin-yue
authors.initials: XY
authors.lastname: Zhang
authors.forename: Yan-quan
authors.initials: YQ
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Wen
authors.forename: Li-ying
authors.initials: LY
authors.lastname: Zhu
mesh_terms: D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009245:NADH Dehydrogenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D013447:Sulfites / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D020543:Proteome; D013447:Sulfites; C030419:andrographolide; D009245:NADH Dehydrogenase; C588033:NdufA10 protein, mouse; C009279:sodium bisulfite