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Effects of edaravone on hypoxic human astrocytes revealed by a proteomic approach

Taigen Sase, Mitsumi Arito, Hidetaka Onodera, Manae S. Kurokawa, Yuichiro Tanaka, Tomohiro Kato

Introduction: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) of a free radical scavenger has been widely used in treatment of acute ischemic stroke. However, effects of edaravone on hypoxic astrocytes have not been fully understood. Therefore, we investigated the effects by proteomic analysis.

Methods: We cultured human astrocytes under hypoxia and normoxia with or without edaravone. Then, we compared protein profiles of the astrocytes using 2-dimensional differential gel electrophoresis (2DDIGE). Further, we identified proteins affected by hypoxia and/or edaravone by mass spectrometry.

Results: We detected 507 protein spots by 2D-DIGE. Among them, intensity of 22 spots showed more than 1.5-fold increase or less than 1/1.5-fold decrease with statistical significance (p<0.05) by hypoxia. We were able to identify 6 out of the 22 protein spots (increased: alpha-enolase (ENO1, from 2 spots) and ephrin-B2, decreased: adenosine triphosphate synthase subunit alpha (ATPA), mitochondrial heat shock 70 kDa protein 1A/1B, and ferritin light chain). In addition, in 61 out of the 507 spots, the spot intensity showed more than 1.3-fold increase or less than 1/1.3-fold decrease with statistical significance (p<0.05) by hypoxia. In 9 out of the 61 spots, the hypoxia-induced intensity alteration was suppressed by the simultaneous addition of edaravone. Three out of the 9 protein spots were identified (ENO1, ATPA, and rab-interacting lysosomal protein-like protein 1).

Conclusion: Edaravone suppressed a part of molecular responses of human astrocytes to hypoxia. Our data would support use of edaravone in acute ischemic stroke.