Changes in redox plasma proteome of Pon1-/- mice are exacerbated by a hyperhomocysteinemic diet

Free Radic Biol Med. 2021 Apr 7:S0891-5849(21)00202-1. doi: 10.1016/j.freeradbiomed.2021.03.042. Online ahead of print.ABSTRACTHigh-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 protei...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Source Type: research