PMID- 25069821
OWN - NLM
STAT- MEDLINE
DCOM- 20151013
LR  - 20141202
IS  - 1096-7206 (Electronic)
IS  - 1096-7192 (Linking)
VI  - 113
IP  - 3
DP  - 2014 Nov
TI  - Paraoxonase 1 deficiency and hyperhomocysteinemia alter the expression of mouse 
      kidney proteins involved in renal disease.
PG  - 200-6
LID - S1096-7192(14)00215-7 [pii]
LID - 10.1016/j.ymgme.2014.07.011 [doi]
AB  - SCOPE: Hyperhomocysteinemia (HHcy) is associated with kidney disease and leads to 
      atherosclerosis and thrombosis. Paraoxonase 1 (Pon1), a hydrolase that 
      participates in homocysteine (Hcy) metabolism and is carried in the circulation 
      on high-density lipoprotein, has also been linked to kidney disease and 
      atherothrombosis. Pon1-knockout mice are susceptible to atherosclerosis and 
      exhibit a kidney-associated phenotype, polyuria or urine dilution. We hypothesize 
      that HHcy and Pon1 deficiency are toxic to kidney function because they impair 
      metabolic pathways important for normal kidney homeostasis. METHODS AND RESULTS: 
      We examined changes in the mouse kidney proteome induced by Pon1 gene deletion 
      and dietary HHcy, using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass 
      spectrometry. We found that the expression of ten mouse kidney proteins was 
      altered by the Pon1(-/-) genotype or HHcy. Proteins involved in metabolism of 
      lipid (ApoA-I), protein (Hspd1), carbohydrate (Pdhb, Fbp1-isoform2, Eno1), and 
      energy (Ndufs8, Ldhd) were down-regulated. Proteins involved in lipid transport 
      (Pebp1), oxidative stress response (Prdx2), and cellular detoxification (Glo1) 
      were up-regulated. The kidney proteins altered by HHcy or Pon1 are also altered 
      in renal disease. CONCLUSION: Our findings suggest that excess Hcy is toxic 
      because it deregulates the expression of proteins involved in diverse cellular 
      processes-from lipid, protein, carbohydrate, and energy metabolisms to 
      detoxification and antioxidant defenses-that are essential for normal kidney 
      homeostasis. Dysregulation of these processes can account for the involvement of 
      HHcy and reduced Pon1 in kidney disease. Our findings also show that Pon1 plays 
      an important role in maintaining normal kidney homeostasis.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Suszynska-Zajczyk, Joanna
AU  - Suszynska-Zajczyk J
AD  - Institute of Bioorganic Chemistry, Poznan, Poland.
FAU - Sikora, Marta
AU  - Sikora M
AD  - Institute of Bioorganic Chemistry, Poznan, Poland.
FAU - Jakubowski, Hieronim
AU  - Jakubowski H
AD  - Institute of Bioorganic Chemistry, Poznan, Poland; Department of Biochemistry and 
      Biotechnology, University of Life Sciences, Poznan, Poland; Department of 
      Microbiology & Molecular Genetics, Rutgers-New Jersey Medical School, 
      International Center for Public Health, Newark, NJ, USA. Electronic address: 
      jakubows@njms.rutgers.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140717
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Proteome)
RN  - EC 3.1.8.1 (Aryldialkylphosphatase)
RN  - EC 3.1.8.1 (PON1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Aryldialkylphosphatase/*deficiency/genetics
MH  - Gene Expression
MH  - Hyperhomocysteinemia/*metabolism
MH  - Kidney/*metabolism
MH  - Mice, Inbred C57BL
MH  - Proteome/metabolism
OTO - NOTNLM
OT  - High-methionine diet
OT  - Hyperhomocysteinemia
OT  - Kidney disease
OT  - Mouse kidney proteome
OT  - Paraoxonase 1
OT  - Polyuria
EDAT- 2014/07/30 06:00
MHDA- 2015/10/16 06:00
CRDT- 2014/07/30 06:00
PHST- 2014/06/04 00:00 [received]
PHST- 2014/07/09 00:00 [revised]
PHST- 2014/07/10 00:00 [accepted]
PHST- 2014/07/30 06:00 [entrez]
PHST- 2014/07/30 06:00 [pubmed]
PHST- 2015/10/16 06:00 [medline]
AID - S1096-7192(14)00215-7 [pii]
AID - 10.1016/j.ymgme.2014.07.011 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2014 Nov;113(3):200-6. doi: 10.1016/j.ymgme.2014.07.011. Epub 
      2014 Jul 17.