The internalization and lysosomal degradation of brain AQP4 after ischemic injury.
The membrane-bound water channel aquaporin-4 (AQP4) plays a significant role in maintaining brain water homeostasis. In ischemic brain, changes in the expression level of AQP4 have been reported. Previous studies suggest that the internalization of several membrane-bound proteins, including AQP4, may occur with or without lysosomal degradation. In this study, the internalization of AQP4 was detected in the ischemic rat brain via double immunofluorescence labeling. Specifically, AQP4 and early endosome antigen-1 (EEA1) co-localized after 1 h post-ischemic injury. Moreover, the co-expression of AQP4 and lysosomal-associated membrane protein-1 (LAMP1) was observed after 3 h post-ischemia. These findings suggest that AQP4 is internalized and the lysosome is involved in degrading the internalized AQP4 in the ischemic brain. AQP4 is known to be downregulated by the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) in vivo and in vitro. The results in this study displayed that PMA infusion could decrease brain edema accompanied by AQP4 downregulation in ischemic brain. However, compared with vehicle infusion, PKC activator infusion did not increase the ratio of internalized or lysosomal degraded AQP4. That is, we have not found out evidence to prove protein kinase C activator PMA can promote the internalization or lysosomal degradation of AQP4 in the ischemic brain.
Institute of Neuroscience, Chongqing Medical University, Chongqing 400016, People's Republic of China; Department of Anatomy, Chongqing Medical University, Chongqing 400016, People's Republic of China.
Juan
J
Huang
Shan Quan
SQ
Sun
Wei Tian
WT
Lu
Jin
J
Xu
Sheng Wei
SW
Gan
Zhen
Z
Chen
Guo Ping
GP
Qiu
Si Qin
SQ
Huang
Fei
F
Zhuo
Qian
Q
Liu
Shi Ye
SY
Xu
D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate
Aquaporin-4; Cerebral ischemia; Endosome; Internalization; Lysosome