title: Arjunolic acid ameliorates reactive oxygen species via inhibition of p47(phox)-serine phosphorylation and mitochondrial dysfunction.
abstract: Impaired cardiovascular function during acute myocardial infarction (MI) is partly associated with recruitment of activated polymorphonuclear neutrophils. The protective role of arjunolic acid (AA; 2,3,23-trihydroxy olean-12-en-28-oic acid) is studied in the modulation of neutrophil functions in vitro by measuring the reactive oxygen species (ROS) generation. Neutrophils were isolated from normal and acute MI mice to find out the efficacy of AA in reducing oxidative stress. Stimulation of neutrophils with phorbol-12-myristate-13-acetate (PMA) resulted in an oxidative burst of superoxide anion (O2(-)) and enhanced release of lysosomal enzymes. The treatment of neutrophils with PMA induced phosphorylation of Ser345 on p47(phox), a cytosolic component of NADPH oxidase. Furthermore, we observed activated ERK induced phosphorylation of Ser345 in MI neutrophils. Treatment with AA significantly inhibited the phosphorylation of P47(phox) and ERK in the stimulated controls and MI neutrophils. Oxidative phosphorylation activities in MI cells were lower than in control, while the glycolysis rates were elevated in MI cells compared to the control. In addition, we observed AA decreased intracellular oxidative stress and reduced the levels of O2(-) in neutrophils. This study therefore identifies targets for AA in activated neutrophils mediated by the MAPK pathway on p47(phox) involved in ROS generation.
authors: Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA.
authors: Sumitra
authors: S
authors: Miriyala
authors: Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA.
authors: Mini
authors: M
authors: Chandra
authors: Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA.
authors: Benjamin
authors: B
authors: Maxey
authors: Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA.
authors: Alicia
authors: A
authors: Day
authors: Graduate Center for Toxicology, University of Kentucky, Lexington, USA.
authors: Daret K
authors: DK
authors: St Clair
authors: Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA; Internal Medicine, University of Kentucky, Lexington, USA. Electronic address: mpanch@lsuhsc.edu.
authors: Manikandan
authors: M
authors: Panchatcharam
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D015398:Signal Transduction; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D014315:Triterpenes; D013481:Superoxides; C061640:arjunolic acid; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013755:Tetradecanoylphorbol Acetate
keywords: Arjunolic acid; Extracellular regulated kinase; NADPH oxidase; Neutrophils; Reactive oxygen species