PMID- 33838286
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20220531
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 169
DP  - 2021 Jun
TI  - Changes in redox plasma proteome of Pon1-/- mice are exacerbated by a 
      hyperhomocysteinemic diet.
PG  - 169-180
LID - S0891-5849(21)00202-1 [pii]
LID - 10.1016/j.freeradbiomed.2021.03.042 [doi]
AB  - High-density lipoprotein (HDL), in addition to promoting reverse cholesterol 
      transport, possesses anti-oxidative, anti-inflammatory, and antithrombotic 
      activities, which are thought to be promoted by paraoxonase 1 (PON1), an 
      HDL-associated enzyme. Reduced levels of PON1 are associated with increased 
      oxidative stress and cardiovascular disease both in humans and Pon1(-/-) mice. 
      However, molecular basis of these associations are not fully understood. We used 
      label-free mass spectrometry and Ingenuity Pathway Analysis bioinformatics 
      resources to examine plasma proteomes in four-month-old Pon1(-/-) mice (n = 32) 
      and their Pon1(+/+) siblings (n = 15) fed with a hyper-homocysteinemic (HHcy) 
      diet. We found that inactivation of the Pon1 gene resulted in dysregulation of 
      proteins involved in the maintenance of redox homeostasis in mice. 
      Redox-responsive proteins affected by Pon1(-/-) genotype were more numerous in 
      mice fed with HHcy diet (18 out of 89, 20%) than in mice fed with a control diet 
      (4 out of 50, 8%). Most of the redox-related proteins affected by Pon1(-/-) 
      genotype in mice fed with a control diet (3 out of 4, 75%) were also affected in 
      HHcy mice, while the majority of Pon1(-/-) genotype-dependent redox proteins in 
      HHcy mice (15 out of 18, 83%) were not affected by Pon1(-/-) genotype in control 
      diet animals. In addition to redox-related proteins, we identified proteins 
      involved in acute phase response, complement/blood coagulation, lipoprotein/lipid 
      metabolism, immune response, purine metabolism, glucose metabolism, and other 
      proteins that were dysregulated by Pon1(-/-) genotype in HHcy mice. Taken 
      together, our findings suggest that Pon1 interacts with proteins involved in 
      antioxidant defenses and other processes linked to cardiovascular disease. 
      Dysregulation of these processes provides an explanation for the pro-oxidant and 
      pro-atherogenic phenotypes observed in Pon1(-/-) mice and humans with attenuated 
      PON1 levels.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Sikora, Marta
AU  - Sikora M
AD  - European Centre for Bioinformatics and Genomics, Institute of Bioorganic 
      Chemistry, 61-704, Poznan, Poland.
FAU - Jakubowski, Hieronim
AU  - Jakubowski H
AD  - Department of Biochemistry and Biotechnology, University of Life Sciences, 
      60-632, Poznan, Poland; Department of Microbiology, Biochemistry and Molecular 
      Genetics, Rutgers University-New Jersey Medical School, International Center for 
      Public Health, Newark, NJ, USA. Electronic address: jakubows@rutgers.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210407
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
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/genetics/metabolism
MH  - Diet
MH  - *Hyperhomocysteinemia/genetics
MH  - Mice
MH  - Oxidation-Reduction
MH  - Proteome
OTO - NOTNLM
OT  - Homocysteine
OT  - Label-free mass spectrometry
OT  - Plasma proteome
OT  - Pon1-KO mice
OT  - Redox homeostasis
EDAT- 2021/04/11 06:00
MHDA- 2021/06/29 06:00
CRDT- 2021/04/10 20:09
PHST- 2021/02/09 00:00 [received]
PHST- 2021/03/28 00:00 [revised]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/04/11 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/04/10 20:09 [entrez]
AID - S0891-5849(21)00202-1 [pii]
AID - 10.1016/j.freeradbiomed.2021.03.042 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2021 Jun;169:169-180. doi: 
      10.1016/j.freeradbiomed.2021.03.042. Epub 2021 Apr 7.