Arjunolic acid ameliorates reactive oxygen species via inhibition of p47phox-serine phosphorylation and mitochondrial dysfunction

Sumitra Miriyala, Mini Chandra, Benjamin Maxey, Alicia Day, Daret K. St. Clair, Manikandan Panchatcharam

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 p47phox, 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 P47phox 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 p47phox involved in ROS generation.

Original languageEnglish
Pages (from-to)70-77
Number of pages8
JournalInternational Journal of Biochemistry and Cell Biology
Volume68
DOIs
StatePublished - Nov 11 2015

Bibliographical note

Funding Information:
The authors wish to thank Ms. Talicia A. Tarver who assisted in the proof reading of the manuscript. This project was supported by grants from NIH ( R25RR026019 and R25OD010954 ); Beginning Grant-in-Aid ( 0950118G ); and a Scientist Development Grant ( 10SDG4190036 ) from the American Heart Association .

Keywords

  • Arjunolic acid
  • Extracellular regulated kinase
  • NADPH oxidase
  • Neutrophils
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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