The dual effects of the astrocyte‐specific enhancer of the <scp>AQP</scp>4 M1 promoter

Abe, Yoichiro; Goda, Wakami; Ikeshima-Kataoka, Hiroko; Yasui, Masato

doi:10.1002/1873-3468.12910

Cited by 3 publications

(2 citation statements)

References 37 publications

(52 reference statements)

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“…Our results show that increased AQP4 is accompanied by increased astrocytes and microvessels ( Figure 4 ). The role of these complex microenvironment changes in the pathogenesis of cerebral ischemia has not been fully elucidated, and the dual role of AQP4 relies on the proportion of subtypes and the change of molecular structure rather than the amount ( Barati Farimani et al, 2014 ; Abe et al, 2017 ; Lisjak et al, 2017 ; Palazzo et al, 2019 ; Simone et al, 2019 ). Sun et al (2022) recently showed that peri-infarct AQP4 polarization correlated positively with the ultra-high b -values of ADC in rat at 14 days after stroke.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity evaluation of multi-high b-value apparent diffusion coefficient on cerebral ischemia in MCAO rat

et al. 2022

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PurposeTo assess brain damage in a rat model of cerebral ischemia based on apparent diffusion coefficient (ADC) data obtained from multi-high b-values and evaluate the relationship between Aquaporin 4 (AQP4) expression and ADC.MethodsThirty eight male Sprague–Dawley rats were randomized into two groups: (1) sham controls (n = 6) and (2) cerebral ischemia (successful model, n = 19). All rats underwent diffusion-weighted imaging (DWI) with both standard b-values and multi-high b-values (2,500–4,500 s/mm2) using a 3.0-T device. Standard ADC (ADCst) maps and multi-high b-value ADCs (ADCmh) were calculated, respectively. Aquaporin 4 expression was quantified using Western blot. Relative values of ADCst and ADCmh, AQP4 expression were compared between the sham group and the ischemia group. Correlations between ADC values and AQP4 expression were evaluated.ResultsAt 0.5 h after suture insertion, the value of ADCmh on the lesion was obviously decreased, and there was no difference in lesion volume when compared with ADCst. After reperfusion, besides similar regions where ADCst values decreased, we also found additional large values on ADCmh within the cortex of the ipsilateral side or surrounding the lesion. The lesion evolution of the large value on ADCmh was quite different from other indicators. But the total ADCmh values were still significantly associated with ADCst. The AQP4 protein expression level was appreciably increased after middle cerebral artery occlusion (MCAO), but there was no correlation between AQP4 expression either with ADCmh or ADCst.ConclusionWe found the large values on ADCmh during the progression of cerebral infarction is varied, but there was no correlation between ADCmh values and AQP4 expression. ADCmh may indicate the heterogeneity of ischemia lesions, but the underlying pathological basis should be further explored.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity evaluation of multi-high b-value apparent diffusion coefficient on cerebral ischemia in MCAO rat

et al. 2022

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“…The role of membrane protein anchoring factors in the OAP assembly is strictly correlated to AQP4 isoform expression. In the natural context the expression pattern of the AQP4 gene in astrocytes includes at least three other isoforms, M1-AQP4 and two C-terminal extended isoforms named M1ex-AQP4 and M23ex-AQP4, generated by finely regulated alternative transcription/promoters [47] and translational control mechanisms [17,41]. The analysis of OAPs at the level of perivascular astrocyte processes has shown that AQP4 is co-expressed and co-localized with C-terminal extended isoforms.…”

Section: Discussionmentioning

confidence: 99%

Host-Cell Type Dependent Features of Recombinant Human Aquaporin-4 Orthogonal Arrays of Particles—New Insights for Structural and Functional Studies

Pisani

Simone

Mola

et al. 2019

Cells

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The CNS plasma-membrane water channel aquaporin-4 (AQP4) is expressed as two major isoforms able to aggregate into supramolecular assemblies known as ‘orthogonal arrays of particles’ (OAPs). OAP subnanometric features are largely unknown mainly because a method for the expression, isolation, and crystallization of integral human OAPs has not been developed. Here, the human OAP-forming isoform M23-AQP4 was expressed in insect and mammalian cell lines and AQP4 and OAP features evaluated. Native size exclusion chromatography was employed to isolate and analyze authentically folded OAPs, and neuromyelitis optica (NMO)-specific sandwich ELISA was developed to test OAP-integrity. The results demonstrate that in insect cells most AQP4 remains intracellular and unfolded and that OAPs are largely disassembled after the detergent extraction step. In mammalian cells, AQP4 showed regular plasma membrane targeting and OAPs exhibited strong post-extraction stability. Starting from the mammalian cell expression system, we isolated authentically folded OAPs. Together these data suggest a new strategy for expressing and isolating integral recombinant human OAPs and providing new insights into the cell-type dependent OAP-assembly and post-extraction stability, potentially useful to design new approaches for structural and functional studies of OAP and for other plasma membrane proteins organized into supramolecular structures.

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Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System

Abe

Yasui

2022

Biomolecules

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Since the discovery of a specific autoantibody in patients with neuromyelitis optica spectrum disorder (NMOSD) in 2004, the water channel aquaporin-4 (AQP4) has attracted attention as a target of autoimmune diseases of the central nervous system. In NMOSD, the autoantibody (NMO-IgG) binds to the extracellular loops of AQP4 as expressed in perivascular astrocytic end-feet and disrupts astrocytes in a complement-dependent manner. NMO-IgG is an excellent marker for distinguishing the disease from other inflammatory demyelinating diseases, such as multiple sclerosis. The unique higher-order structure of AQP4—called orthogonal arrays of particles (OAPs)—as well as its subcellular localization may play a crucial role in the pathogenesis of the disease. Recent studies have also demonstrated complement-independent cytotoxic effects of NMO-IgG. Antibody-induced endocytosis of AQP4 has been suggested to be involved in this mechanism. This review focuses on the binding properties of antibodies that recognize the extracellular region of AQP4 and the characteristics of AQP4 that are implicated in the pathogenesis of NMOSD.

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The dual effects of the astrocyte‐specific enhancer of the AQP4 M1 promoter

Cited by 3 publications

References 37 publications

Heterogeneity evaluation of multi-high b-value apparent diffusion coefficient on cerebral ischemia in MCAO rat

Heterogeneity evaluation of multi-high b-value apparent diffusion coefficient on cerebral ischemia in MCAO rat

Host-Cell Type Dependent Features of Recombinant Human Aquaporin-4 Orthogonal Arrays of Particles—New Insights for Structural and Functional Studies

Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System

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