Testosterone up‐regulates aquaporin‐4 expression in cultured astrocytes

Gu, Feng; Hata, Ryuji; Toku, Kazuko; Yang, Lihua; Jie, Yong; Maeda, Nobuji; Sakanaka, Masahiro; Tanaka, Junya

doi:10.1002/jnr.10603

Cited by 60 publications

(52 citation statements)

References 41 publications

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“…Although the mechanism for AQP4 upregulation in these disease states has yet to be determined, evidence from astrocyte cell culture experiments suggest that AQP4 may be upregulated by changes in extracellular osmolality (Arima et al, 2003) and hormonal factors (Gu et al, 2003). In addition, reactive astrocytosis induced by inflammatory cytokines is often associated with increased AQP4 (Badaut et al, 2003;Bloch et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Accelerated Progression of Kaolin-Induced Hydrocephalus in Aquaporin-4-Deficient Mice

Bloch¹,

Auguste

Manley

et al. 2006

J Cereb Blood Flow Metab

178

138

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Hydrocephalus is caused by an imbalance in cerebrospinal fluid (CSF) production and absorption, resulting in excess ventricular fluid accumulation and neurologic impairment. Current therapy for hydrocephalus involves surgical diversion of excess ventricular fluid. The water-transporting protein aquaporin-4 (AQP4) is expressed at the brain-CSF and blood-brain barriers. Here, we provide evidence for AQP4-facilitated CSF absorption in hydrocephalus by a transparenchymal pathway into the cerebral vasculature. A mouse model of obstructive hydrocephalus was created by injecting kaolin (2.5 mg/mouse) into the cisterna magna. Intracranial pressure (ICP) was B5 mm Hg and ventricular size < 0.3 mm 3 in control mice. Lateral ventricle volume increased to 3.760.5 and 5.1 60.5 mm 3 in AQP4 null mice at 3 and 5 days after injection, respectively, significantly greater than 2.6 60.3 and 3.560.5 mm 3 in wildtype mice (P < 0.005). The corresponding ICP was 2262 mm Hg at 3 days in AQP4 null mice, significantly greater than 1461 mm Hg in wildtype mice (P < 0.005). Brain parenchymal water content increased by 2% to 3% by 3 days, corresponding to B50 lL of fluid, indicating backflow of CSF from the ventricle into the parenchymal extracellular space. A multicompartment model of hydrocephalus based on experimental data from wildtype mice accurately reproduced the greater severity of hydrocephalus in AQP4 null mice, and predicted a much reduced severity if AQP4 expression/function were increased. Our results indicate a significant role for AQP4-mediated transparenchymal CSF absorption in hydrocephalus and provide a rational basis for evaluation of AQP4 induction as a nonsurgical therapy for hydrocephalus.

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Section: Discussionmentioning

confidence: 99%

Accelerated Progression of Kaolin-Induced Hydrocephalus in Aquaporin-4-Deficient Mice

Bloch¹,

Auguste

Manley

et al. 2006

J Cereb Blood Flow Metab

178

138

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“…Estrogen was found to directly affect AQP expression in the kidney. 23,24 Meanwhile, testosterone has been found to up-regulate expression of AQP-4 in astrocytes 25 and AQP-1 26,27 and AQP-7 27 in uterus. In this study, AQP-2 expression in the kidney was markedly increased under testosterone influence.…”

Section: Discussionmentioning

confidence: 99%

Effects of gonadectomy and testosterone treatment on aquaporin expression in the kidney of normotensive and hypertensive rats

Loh

Giribabu

Salleh

2017

Exp Biol Med (Maywood)

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We tested the hypothesis that testosterone-induced increase in blood pressure was due to changes in aquaporin (AQP) expression in kidneys. In this study, expression level of kidney AQPs was investigated under testosterone influence. Adult normotensive Wistar Kyoto (WKY) and hypertensive SHR male and female rats underwent gonadectomy. For female rats, testosterone was given for six weeks duration, two weeks following ovariectomy via subcutaneous silastic implant. Mean arterial pressure (MAP) was measured in all the rats after eight weeks via carotid artery cannulation and the rats were then sacrificed and kidneys were harvested for analyses of AQP-1, 2, 3, 4, 6, and 7 mRNA and protein expressions by quantitative real-time PCR and Western blotting, respectively. Distribution of AQP subunits' protein in kidneys was observed by immunofluorescence. In male WKY rats, MAP, AQP-1, 2, 4, and 7 protein; and mRNA expression decreased however AQP-3 protein and mRNA expression increased following orchidectomy. The vice versa effects were observed in testosterone-treated ovariectomized female WKY rats. However, no changes in AQP-6 expression were observed. Meanwhile, in adult male SHR rats, MAP and expression level of all AQP subunits decreased following orchidectomy. The opposite effects were seen in ovariectomized female SHR rats following testosterone treatment. Immunofluorescence study showed AQP-1 and AQP-7 were distributed in the proximal convoluted tubules (PCT) while AQP-2, AQP-4, and AQP-6 were distributed in the collecting ducts (CDs). AQP-3 was distributed in the PCT and CD. In conclusion, changes in AQP subunit expression in kidneys could explain changes in blood pressure under testosterone influence. Impact statement This study provides fundamental understanding on the mechanisms underlying testosterone-induced increase in blood pressure which involve regulation of aquaporin channel subunits in the kidneys. A better understanding of this issue can help to explain the reason for higher blood pressure in males as compared to females and may explain the reason for higher blood pressure in females after menopause than females before menopause, the former most probably related to the changes in female androgen.

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“…The biophysical properties and activity of Kir and AQP channels are modified by diverse protein kinases and regulatory molecules (45)(46)(47)(48). The association of the DGC with signaling molecules, including neuronal nitric-oxide synthase (30), syntrophin-associated serine/threonine kinase, and Grb2 (31,35,49), has been described.…”

Section: Figmentioning

confidence: 99%

The Potassium Channel Kir4.1 Associates with the Dystrophin-Glycoprotein Complex via α-Syntrophin in Glia

Connors

Adams

Froehner

et al. 2004

Journal of Biological Chemistry

174

134

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One of the major physiological roles of potassium channels in glial cells is to promote "potassium spatial buffering" in the central nervous system, a process necessary to maintain an optimal potassium concentration in the extracellular environment. This process requires the precise distribution of potassium channels accumulated at high density in discrete subdomains of glial cell membranes. To obtain a better understanding of how glial cells selectively target potassium channels to discrete membrane subdomains, we addressed the question of whether the glial inwardly rectifying potassium channel Kir4.1 associates with the dystrophin-glycoprotein complex (DGC). Immunoprecipitation experiments revealed that Kir4.1 is associated with the DGC in mouse brain and cultured cortical astrocytes. In vitro immunoprecipitation and pull-down assays demonstrated that Kir4.1 can bind directly to ␣-syntrophin, requiring the presence of the last three amino acids of the channel (SNV), a consensus PDZ domain-binding motif. Furthermore, Kir4.1 failed to associate with the DGC in brains from ␣-syntrophin knockout mice. These results suggest that Kir4.1 is localized in glial cells by its association with the DGC through a PDZ domain-mediated interaction with ␣-syntrophin and suggest an important role for the DGC in central nervous system physiology.

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Testosterone up‐regulates aquaporin‐4 expression in cultured astrocytes

Cited by 60 publications

References 41 publications

Accelerated Progression of Kaolin-Induced Hydrocephalus in Aquaporin-4-Deficient Mice

Accelerated Progression of Kaolin-Induced Hydrocephalus in Aquaporin-4-Deficient Mice

Effects of gonadectomy and testosterone treatment on aquaporin expression in the kidney of normotensive and hypertensive rats

The Potassium Channel Kir4.1 Associates with the Dystrophin-Glycoprotein Complex via α-Syntrophin in Glia

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