title: Lactic acid increases aquaporin 4 expression on the cell membrane of cultured rat astrocytes.
abstract: The water channel protein aquaporin (AQP) may play roles in the homeostasis of water content in the brain and brain edema. One possible mechanism of brain edema is glial swelling due to lactic acidosis associated with ischemia. Here, we investigated the effect of lactic acid on the expression and cellular distribution of AQP 4 in cultured rat astrocytes. After 24h of incubation, the AQP4 expression level increased maximally with 35mM lactic acid. The AQP4 expression levels also increased with hydrochloric acid or acetic acid. In contrast, with sodium lactate, the AQP4 levels did not increase. The increase in AQP4 expression level occurred without a significant increase in AQP4 mRNA expression level by lactic acid. Under the conditions of de novo protein synthesis inhibition with cycloheximide, lactic acid increased the AQP4 expression level. Furthermore, lactic acid increased the AQP4 expression level on the cell surface of the astrocytes, as determined by a cell surface biotinylation assay and immunocytochemical examination. The increase in AQP4 expression level on the cell membrane of astrocytes induced by lactic acid may be a new regulation mechanism of AQP4 in the brain.
authors.affiliation: Department of Anesthesiology and Medical Crisis Management, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Morishima
authors.forename: Mineyoshi
authors.initials: M
authors.lastname: Aoyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iida
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hirate
authors.forename: Hajime
authors.initials: H
authors.lastname: Arima
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasano
authors.forename: Takako
authors.initials: T
authors.lastname: Tsuda
authors.forename: Hirotada
authors.initials: H
authors.lastname: Katsuya
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Asai
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sobue
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000143:Acids / Q000494:pharmacology; D000818:Animals; D051401:Aquaporin 4 / Q000096:biosynthesis*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D019921:Biotinylation; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000143:Acids; D051401:Aquaporin 4; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D019344:Lactic Acid; D003513:Cycloheximide