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Methionine sulfoxide reductase as a neuroprotective mechanism in a model of anoxia tolerance: Trachemys scripta
Author(s) -
Reiterer Melissa,
Milton Sarah L.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1075.4
Subject(s) - msra , methionine sulfoxide reductase , reactive oxygen species , methionine , oxidative stress , neuroprotection , biochemistry , biology , antioxidant , microbiology and biotechnology , chemistry , amino acid , pharmacology
The damaging effects of oxidative stress caused by the accumulation of Reactive Oxygen Species (ROS) have been linked to several neurodegenerative diseases as well as aging and senescence. Mammals and especially humans are extremely susceptible to this damage as can be observed following an ischemic stroke when blood flow is restored and oxygen is reintroduced. ROS damage lipids, proteins, and DNA, and thus can induce further cell death beyond that caused by the ischemia. However, some organisms can withstand extended anoxia and reoxygenation without damage, including the freshwater turtle Trachemys scripta . To cope with potential oxidative stress, the freshwater turtle possesses high endogenous levels of antioxidants and can also inhibit ROS production. One potential antioxidant mechanism is the Methionine Sulfoxide Reductase System (Msr) that catalyzes the reduction of oxidized Methionine (Met) residues. Methionine residues are easily oxidized amino acids; oxidized Met is associated with decreased protein activity and Msr may restore function to damaged proteins; it has also been shown to scavenge ROS and thus ameliorates cellular damage. The present study investigated the role and regulation of MsrA in turtle neuronal cultures exposed to 4 hours of anoxia/4 hours of reoxygenation by altering the expression of MsrA. As FOXO3a has been shown to regulate MsrA levels in other animal models, we also induced its expression by transfecting a FOXO3a plasmid into the cells. We found that knock down of MsrA expression with target specific siRNA resulted in decreased cell viability; and induction of FOXO3a showed protection against cell death. Furthermore, treatment of cells with Epigallocatechin gallate (EGCG), an extract found in green tea that has antioxidant properties, results in increased expression of FOXO3a. These results suggest that MsrA may play an important role in protection against anoxia and oxidative stress in the turtle brain, and may prove to be a target to treat diseases of ischemia. Support or Funding Information Florida Atlantic University GRIP Grant (2015–2016) John Nambu Scholarship for Molecular Biology (FAU‐ 2016) Andrew Todd Auster Alumni Scholarship (FAU‐2016)