cilostazol enhances oxidative glucose metabolism in both neurons and astroglia without increasing ros production西洛地唑提高氧化葡萄糖代谢在神经元和星形神经胶质不增加活性氧的生产.pdfVIP

Pharmacology Pharmacy, 2011, 2, 315-321 315 doi:10.4236/pp.2011.24040 Published Online October 2011 (http://www.SciRP.org/journal/pp) Cilostazol Enhances Oxidative Glucose Metabolism in Both Neurons and Astroglia without Increasing Ros Production * Shinichi Takahashi , Yoshikane Izawa, Norihiro Suzuki Department of Neurology, Keio University School of Medicine, Tokyo, Japan. * Email: takashin@tka.att.ne.jp R Received August 5th, 2011; revised September 13th, 2011; accepted September 25th, 2011. ABSTRACT Cilostazol, a potent inhibitor of type 3 phosphodiesterase (PDE3), has recently been reported to exert neuroprotective effects during acute cerebral ischemic injury. These effects are, at least in part, mediated by the inhibition of oxidative cell death. However, the effects of cilostazol on glucose metabolism in brain cells have not been determined. In the pre- sent study, we examined the effects of cilostazol on the oxidative metabolism of glucose and the resultant formation of reactive oxygen species (ROS) in cultured neurons and astroglia. Cultures of neurons or astroglia were prepared from Sprague-Dawley rats. The cells were treated with cilostazol (0 - 30 μM) for 48 hours prior to the assay. L-[U-14C]lactate ([14C]lactate) or [1-14C]pyruvate ([14C]pyruvate ) oxidation was measured. ROS production was determined using an H2DCFDA assay with a microplate reader. Forty-eight hours of exposure to cilostazol resulted in dose-dependent in- creases in [14C]lactate and [14C]pyruvate oxidation in both the neurons and astroglia. Dibutyryl cyclic AMP (0 - 0.5 mM) also increased [14C]lactate oxidation, indicating cAMP-mediated PDH activation. In contrast,free radical forma- tion was not affected by cilostazol in either the neurons or astroglia. Cilostazol enhanced the oxidative metabolism of gl