title: Internalization of aquaporin-4 after collagenase-induced intracerebral hemorrhage.
abstract: Brain edema formation following intracerebral hemorrhage (ICH) appears to be related with aquaporin-4 (AQP4), which is critically involved in brain volume homeostasis and water balance. Despite its importance, the regulation of AQP4 expression involved in transmembrane water movements still remains rudimentary. Many studies suggest that the internalization of several membrane-bound proteins, including AQP4, may occur with or without lysosomal degradation. Previously, we investigated the internalization of AQP4 in retinal ischemic-reperfusion model. Here, we test the hypothesis that AQP4 is internalized post-ICH and then degraded in the lysosome. The results demonstrated that both AQP4 and the mannose-6-phosphate receptor (MPR) co-localized in perihematomal region at 6 hr post-ICH. In addition, AQP4 and lysosomal-associated membrane protein 1 (LAMP1) also co-localized in perihematomal region, with co-expression increasing followed by a gradual decrease at different time windows post-ICH (6, 12, 24, 48, and 72 hr). After ICH, the Evans blue leakage happened very early at 1 hr and the brain swelling occurred at 3 hr. Moreover, we also found the AQP4 mRNA and AQP4 protein were increased post-ICH. These results suggest that AQP4 is internalized and the lysosome is involved in degrading the internalized AQP4 post-ICH. Both the AQP4 internalization and lysosomal degradation may provide biophysical insights regarding the potential of new treatments for brain edema.
authors.affiliation: Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Qiu
authors.forename: Juan
authors.initials: J
authors.lastname: Huang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Shan-Quan
authors.initials: SQ
authors.lastname: Sun
authors.forename: Sheng-Wei
authors.initials: SW
authors.lastname: Gan
authors.forename: Wei-Tian
authors.initials: WT
authors.lastname: Lu
authors.forename: Ke-Jian
authors.initials: KJ
authors.lastname: Wang
authors.forename: Si-Qin
authors.initials: SQ
authors.lastname: Huang
authors.forename: Shu-Juan
authors.initials: SJ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001929:Brain Edema / Q000378:metabolism*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000378:metabolism*; D017364:Collagenases; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D051401:Aquaporin 4; D017364:Collagenases; D051907:Lysosomal Membrane Proteins; D017527:Receptor, IGF Type 2; C496032:Aqp4 protein, rat; C489117:Lamp1 protein, rat; D052118:Lysosomal-Associated Membrane Protein 1; C034304:cation-dependent mannose-6-phosphate receptor
keywords: aquaporin-4; endosome; internalization; intracerebral hemorrhage; lysosome