Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes.
The membrane pore proteins, aquaporins (AQPs), facilitate the osmotically driven passage of water and, in some instances, small solutes. Under hyperosmotic conditions, the expression of some AQPs changes, and some studies have shown that the expression of AQP1 and AQP5 is regulated by MAPKs. However, the mechanisms regulating the expression of AQP4 and AQP9 induced by hyperosmotic stress are poorly understood. In this study, we observed that hyperosmotic stress induced by mannitol increased the expression of AQP4 and AQP9 in cultured rat astrocytes, and intraperitoneal infusion of mannitol increased AQP4 and AQP9 in the rat brain cortex. In addition, a p38 MAPK inhibitor, but not ERK and JNK inhibitors, suppressed their expression in cultured astrocytes. AQPs play important roles in maintaining brain homeostasis. The expression of AQP4 and AQP9 in astrocytes changes after brain ischemia or traumatic injury, and some studies have shown that p38 MAPK in astrocytes is activated under similar conditions. Since mannitol is commonly used to reduce brain edema, understanding the regulation of AQPs and p38 MAPK in astrocytes under hyperosmotic conditions induced with mannitol may lead to a control of water movements and a new treatment for brain edema.
Arima
Hajime
H
Department of Anesthesia and Critical Care, Okazaki City Hospital, 3-1 Goshoai, Koryuji-cho, Okazaki 444-8553, Japan. arima@sb.starcat.ne.jp
Yamamoto
Naoki
N
Sobue
Kazuya
K
Umenishi
Fuminori
F
Tada
Toyohiro
T
Katsuya
Hirotada
H
Asai
Kiyofumi
K
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D051401:Aquaporin 4; D020346:Aquaporins / Q000235:genetics*; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000008:administration & dosage; D015151:Immunoblotting; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000008:administration & dosage*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
C496030:AQP4 protein, human; C109669:AQP9 protein, human; C496032:Aqp4 protein, rat; C491637:Aqp9 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D006982:Hypertonic Solutions; D012333:RNA, Messenger; D008353:Mannitol; D000841:Anisomycin; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases