| Budget Amount *help |
¥44,720,000 (Direct Cost: ¥34,400,000、Indirect Cost: ¥10,320,000)
Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2010: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Fiscal Year 2009: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2008: ¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
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| Research Abstract |
Reactive oxygen species(ROS) induce chemokines responsible for the recruitment of inflammatory cells at inflamed sites in injury or infection. Here, we demonstrate that the plasma membrane Ca^2-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. TRPM2 Ca^2 influx controls the ROS-induced signal cascade responsible for chemokine production which aggravates inflammation. On the other hand, Oxygen(O_2) intake is tightly controlled in order to secure energy production while minimizing the risk of oxidative damage in aerobic organisms. Mammals' respiratory systems have evolved to respond to changes in O_2 availability via the carotid body and other chemoreceptors. Here, our functional examination of the TRP cation channels expressed in mouse vagal chemoreceptors reveals that the TRPA1 channel is activated by O2 and mediates ionic currents in hyperoxia via its prominent sensitivity to cysteine-mediated oxidation. TRPA1 is also activated in hypoxia through relief from O_2-dependent inhibition by prolyl hydroxylases. Hyperoxia-and hypoxia-induced vagal afferent nerve activities and their consequent ventilatory responses are are controlled by TRPA1. Thus, TRPA1 is an O_2 sensor that regulates O_2supply in vivo.
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