血管收缩
内皮素
内皮素1
血管痉挛
二十烷酸
内分泌学
内科学
生物
SOD2
医学
蛛网膜下腔出血
氧化应激
受体
生物化学
超氧化物歧化酶
花生四烯酸
酶
作者
Justin S. Bickford,Narjis F. Ali,Jerelyn Nick,Musab Al-Yahia,Dawn E. Beachy,Sylvain Doré,Harry S. Nick,Michael F. Waters
标识
DOI:10.1016/j.brainres.2014.09.022
摘要
Endothelins are potent vasoconstrictors and signaling molecules. Their effects are broad, impacting processes ranging from neurovascular and cardiovascular health to cell migration and survival. In stroke, traumatic brain injury or subarachnoid hemorrhage, endothelin-1 (ET-1) is induced resulting in cerebral vasospasm, ischemia, reperfusion and the activation of various pathways. Given the central role that ET-1 plays in these patients and to identify the downstream molecular events specific to transient vasoconstriction, we studied the consequences of ET-1-mediated vasoconstriction of the middle cerebral artery in a rat model. Our observations demonstrate that ET-1 can lead to increases in gene expression, including genes associated with the inflammatory response (Ifnb, Il6, Tnf) and oxidative stress (Hif1a, Myc, Sod2). We also observed inductions (>2 fold) of genes involved in eicosanoid biosynthesis (Pla2g4a, Pla2g4b, Ptgs2, Ptgis, Alox12, Alox15), heme metabolism (Hpx, Hmox1, Prdx1) and iron homeostasis (Hamp, Tf). Our findings demonstrate that mRNA levels for the hormone hepcidin (Hamp) are induced in the brain in response to ET-1, providing a novel target in the treatment of multiple conditions. These changes on the ipsilateral side were also accompanied by corresponding changes in a subset of genes in the contralateral hemisphere. Understanding ET-1-mediated events at the molecular level may lead to better treatments for neurological diseases and provide significant impact on neurological function, morbidity and mortality.
科研通智能强力驱动
Strongly Powered by AbleSci AI