Hyperosmolar Mannitol Stimulates Expression of Aquaporins 4 and 9 through a p38 Mitogen-activated Protein Kinase-dependent Pathway in Rat Astrocytes

Arima, Hisatomi; Yamamoto, Naoki; Sobue, Kazuya; Umenishi, Fuminori; Tada, Toyohiro; Hikita, Katsuya; Asai, Kiyofumi

doi:10.1074/jbc.m304368200

Cited by 154 publications

(113 citation statements)

References 56 publications

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“…Similar to results of the present study, p38, ERK1/2, and JNK MAPK activation by hypertonicity has been demonstrated in inner medullary collecting duct cells and in cells of the medullary thick ascending limb of Henle's loop (43)(44)(45). A role of p38, ERK and JNK in the transcriptional regulation of various aquaporins by hypertonicity has been shown in renal and lung epithelial cells and in astrocytes (45)(46)(47). Data from our present study indicate that MAPKs additionally participate in the accumulation of AQP2 at the plasma membrane, but not at the TGN, in renal CD principal cells immediately following hypertonic challenge.…”

Section: Discussionsupporting

confidence: 77%

Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells

Hasler

Nunes²,

Bouley³

et al. 2008

Journal of Biological Chemistry

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The unique phenotype of renal medullary cells allows them to survive and functionally adapt to changes of interstitial osmolality/tonicity. We investigated the effects of acute hypertonic challenge on AQP2 (aquaporin-2) water channel trafficking. In the absence of vasopressin, hypertonicity alone induced rapid (<10 min) plasma membrane accumulation of AQP2 in rat kidney collecting duct principal cells in situ, and in several kidney epithelial lines. Confocal microscopy revealed that AQP2 also accumulated in the trans-Golgi network (TGN) following hypertonic challenge. AQP2 mutants that mimic the Ser 256 -phosphorylated and -nonphosphorylated state accumulated at the cell surface and TGN, respectively. Hypertonicity did not induce a change in cytosolic cAMP concentration, but inhibition of either calmodulin or cAMP-dependent protein kinase A activity blunted the hypertonicity-induced increase of AQP2 cell surface expression. Hypertonicity increased p38, ERK1/2, and JNK MAPK activity. Inhibiting MAPK activity abolished hypertonicity-induced accumulation of AQP2 at the cell surface but did not affect either vasopressin-dependent AQP2 trafficking or hypertonicity-induced AQP2 accumulation in the TGN. Finally, increased AQP2 cell surface expression induced by hypertonicity largely resulted from a reduction in endocytosis but not from an increase in exocytosis. These data indicate that acute hypertonicity profoundly alters AQP2 trafficking and that hypertonicity-induced AQP2 accumulation at the cell surface depends on MAP kinase activity. This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity.Most mammalian cells are exposed to an extracellular environment that remains isotonic under normal physiological conditions, largely as a result of renal regulatory mechanisms that maintain water and electrolyte body fluid composition within a very narrow range. This process relies on the countercurrent concentration mechanism that occurs along the loop of Henle and which, in turn, depends on the generation of a NaCl and urea concentration gradient along the cortico-papillary axis. As a consequence, renal medullary cells are physiologically exposed to changing conditions of variable interstitial osmolality/tonicity that can reach up to 1200 mosmol/kg in human inner medulla and up to 4500 mosmol/kg in some remarkable rodent species that are adapted to life in arid desert conditions (1). The unique phenotype of these cells allows them to survive and function under these "hostile" conditions and to rapidly adapt to recurrent variations in their environmental tonicity that follow physiological and behavioral changes. In addition to the promotion of intracellular events that ensure cell survival, hypertonicity also promotes events that mediate changes in cell function in various physiological settings. Both rapid and slow responses mediate cell adaptation to increased extracellular tonicity. Rapid responses include actin and micr...

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Section: Discussionsupporting

confidence: 77%

Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells

Hasler

Nunes²,

Bouley³

et al. 2008

Journal of Biological Chemistry

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show abstract

“…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

180

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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“…Although we have shown that miR-130a functions as a transcriptional regulator of AQP4, previous reports on the promoter of AQP4 M1 suggested the presence of an E-box region that acted as a suppressor (20,28). Umenishi and Verkman (21) considered the E-box region to play a crucial role in the transcriptional suppression of the promoter.…”

Section: Mir-130a Represses Transcriptional Activity Of Aqp4 M1mentioning

confidence: 99%

MicroRNA-130a Represses Transcriptional Activity of Aquaporin 4 M1 Promoter

Sepramaniam

Ying

Armugam

et al. 2012

Journal of Biological Chemistry

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Background: Aquaporin 4 has been implicated in fluid homeostasis and imbalance during cerebral ischemia. The M1 isoform of AQP4 is found to be highly expressed in cerebral ischemia. Results: AQP4 M1 transcript is observed to be highly modulated by miR-130a during brain edema. Conclusion: miR-130a is a transcriptional repressor of AQP4 M1 promoter. Significance: miR-130a could be useful in regulating AQP4 expression in brain ischemia.

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Hyperosmolar Mannitol Stimulates Expression of Aquaporins 4 and 9 through a p38 Mitogen-activated Protein Kinase-dependent Pathway in Rat Astrocytes

Cited by 154 publications

References 56 publications

Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells

Acute Hypertonicity Alters Aquaporin-2 Trafficking and Induces a MAPK-dependent Accumulation at the Plasma Membrane of Renal Epithelial Cells

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

MicroRNA-130a Represses Transcriptional Activity of Aquaporin 4 M1 Promoter

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