tailieunhanh - Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM) because it is the origin of a life-and-death signal that sequentially increases (pro-life) and decreases (pro-death) to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1) may play a pro-life role as an interposing signal. | Dai et al. Journal of Biomedical Science 2010 17 72 http content 17 1 72 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I protein kinase G signaling at rostral ventrolateral medulla Kuang-Yu Dai Samuel HH Chan Alice YW Chang Abstract Background Despite its clinical importance a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla RVLM because it is the origin of a life-and-death signal that sequentially increases pro-life and decreases pro-death to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 HO-1 may play a pro-life role as an interposing signal between hypoxiainducible factor-1 HIF-1 and nitric oxide synthase I NOS I protein kinase G PKG cascade in RVLM which sustains central cardiovascular regulatory functions during brain stem death. Methods We performed cardiovascular pharmacological biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos Mev 10 nmol bilaterally into RVLM of adult male Sprague-Dawley rats. Results Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1a or HIF-1P in RVLM. On the other hand the cytoplasmic presence of HO-2 in .