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Inactivation of the glyoxalase anti‐glycation system in porcine brain post‐cardiac arrest and its preservation by pyruvate
Author(s) -
Scott Gary Frank,
Cherry Brandon H,
Williams Arthur,
Ryou MyoungGwi,
Nguyen Anh,
Mallet Robert T
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.981.4
Subject(s) - methylglyoxal , glycation , chemistry , oxidative stress , lactoylglutathione lyase , pyruvic acid , biochemistry , medicine , glutathione , endocrinology , enzyme , receptor
Background Glyoxalase‐1 (GLO1) degrades the toxic glycolytic byproduct methylglyoxal, thereby preventing irreversible glycation of proteins and nucleic acids. However, the glyoxalase system may be inactivated by oxidative stress. Cardiac arrest (CA) and cardiocerebral resuscitation (CCR) provokes intense oxidative stress in the brain. However, the impact of CA/CCR on the brain's anti‐glycation machinery is unknown. Purpose To analyze the impact of ischemia‐reperfusion on the cerebrocortical glyoxalase system in a porcine model of CA/CCR, and to determine the ability of the natural antioxidant pyruvate to protect this crucial anti‐glycation system. Methods Domestic pigs (25–35 kg) were subjected to 10 min CA, followed by 4 min closed‐chest CCR, defibrillation and 4 h recovery. Sodium pyruvate (Figures: Pyr) or NaCl control was infused iv to 3.5–4 mM during CA/CCR and the first 60 min recovery. GLO1 content, activities of GLO1 and glutathione reductase (GR), and protein glycation (Arg‐pyrimidine immunoblot) were analyzed in frontal cortical homogenates collected at 4 h recovery. Results Compared with non‐arrested sham pigs ( n =4), GLO1 content and GLO1 and GR activities ( Figures 1– 3) fell sharply after CA/CCR ( n =4), but were preserved by pyruvate ( n =4). Also, CA/CCR caused protein glycation, particularly at 65 kDa, the MW of the blood‐brain‐barrier component occludin, while pyruvate reversed this glycation. Conclusions Cardiac arrest‐resuscitation impaired the brain's GLO1/GR anti‐glycation defenses in a manner prevented by pyruvate treatment. Thus, the brain's GLO1 system is disabled by acute ischemia‐reperfusion, yet pyruvate intervention protected this pivotal, cerebroprotective system. Support or Funding Information NS076975 National Institute of Neurological Disorders and Stroke