Enhanced expression of aquaporin 4 in human brain with infarction

Aoki, Kazuko; Uchihara, Toshiki; Tsuchiya, Kuniaki; Nakamura, Ayako; Ikeda, Kenji; Wakayama, Yoshihiro

doi:10.1007/s00401-003-0709-y

Cited by 115 publications

(58 citation statements)

References 20 publications

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“…AQP-4 is present in astrocyte endfeet around the vessels, the cells lining the subarachnoid space, and ventricles in the brains under normal condition [54]. Our immunohistochemical study confirmed this distribution in the rat brain.…”

Section: Discussionsupporting

confidence: 82%

The expression and the role of protease nexin-1 on brain edema after intracerebral hemorrhage

Zhao

et al. 2008

Journal of the Neurological Sciences

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Section: Discussionsupporting

confidence: 82%

The expression and the role of protease nexin-1 on brain edema after intracerebral hemorrhage

Zhao

et al. 2008

Journal of the Neurological Sciences

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“…The resultant putative dysfunction of neurovascular coupling then sustains, if not worsens, the chronic low grade ischemia observed in the stroke-prone, hypertensive rat strain, which coupled with AQP4-mediated cytogenic edema, together contribute to stroke-susceptibility. These hypotheses are supported by observations of increased AQP4 in strokeprone SHRSP rats (35) and in poststroke human brains with cerebral infarction (36), and by the detection of a hypoxia inducible factor-1α response element in the 5′ flanking region of the human AQP4 gene.…”

Section: Insight Into Putative Stroke-prone Pathogenic Mechanismssupporting

confidence: 65%

Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic[hCETP]-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats

Bergerat

Decano

et al. 2011

Mol Med

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Stroke is the third leading cause of death in the United States with high rates of morbidity among survivors. The search to fill the unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of animal models of spontaneous stroke in the prestroke stage. Since brain microvessels play key roles in neurovascular coupling, we investigated prestroke microvascular proteome changes. Proteomic analysis of cerebral cortical microvessels (cMVs) was done by tandem mass spectrometry comparing two prestroke time points. Metaprotein-pathway analyses of proteomic spectral count data were done to identify risk factor-induced changes, followed by QSPEC-analyses of individual protein changes associated with increased stroke susceptibility. We report 26 cMV proteome profiles from male and female stroke-prone and non-stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibility. Altogether, proteomic analysis demonstrates significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and postischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much needed novel diagnostic and therapeutic approaches for stroke.

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“…In the brain, AQP1 is concentrated around the apical membrane of the choroid plexus epithelia and moderately present in the hippocampus and ependymal cells (30). Expression of AQP4 is extensive in the astrocytic processes adjacent to cerebral capillaries and in the pial membranes lining the subarachnoid space (31). The expression of these two water channels at strategic locations in the brain emphasizes their importance in cerebral water transport.…”

Section: Figure 3 Expression Of Aqp1 and Aqp4 In Astrocytoma Cells Smentioning

confidence: 99%

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

Sepramaniam

Armugam

Lim

et al. 2010

Journal of Biological Chemistry

137

112

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Aquaporins facilitate efficient diffusion of water across cellular membranes, and water homeostasis is critically important in conditions such as cerebral edema. Changes in aquaporin 1 and 4 expression in the brain are associated with cerebral edema, and the lack of water channel modulators is often highlighted. Here we present evidence of an endogenous modulator of aquaporin 1 and 4. We identify miR-320a as a potential modulator of aquaporin 1 and 4 and explore the possibility of using miR-320a to alter the expression of aquaporin 1 and 4 in normal and ischemic conditions. We show that precursor miR-320a can function as an inhibitor, whereas anti-miR-320a can act as an activator of aquaporin 1 and 4 expressions. We have also shown that antimiR-320a could bring about a reduction of infarct volume in cerebral ischemia with a concomitant increase in aquaporins 1 and 4 mRNA and protein expression. MicroRNAs (miRNAs)2 regulate mRNA expression by binding to the 3Ј-UTR (1). As simple as it sounds, identifying targets for miRNAs remains a challenging task mainly because each miRNA has hundreds of mRNA targets (2). Increasing this complexity are emerging reports on miRNAs binding at 5Ј-UTR as well as promoter regions (3-5). Recent studies also reveal the possibility of miRNAs functioning as transcriptional or splicing regulators within the nucleus (6) and being involved in genetic exchange via exosomes with adjacent cells (7). Because of this complexity in regulation, of the hundreds of miRNAs identified in the human species, only a handful have been assigned their specific targets.Comparison of miRNA profiles between normal and diseased samples allows the identification of crucial miRNAs that are altered during disease conditions and enables one to search for possibilities of altering these expression profiles in an attempt to normalize or reduce the patho-physiological conditions of the disease. Changes in the expression of miRNAs have been reported in several diseases (8 -10) including cerebral ischemia (11-13). Cerebral ischemia is a highly debilitating condition, and ischemia-induced edema further increases complications and morbidity (14). The movement of water into and out of an ischemic brain is thought to be mainly modulated by aquaporins (AQPs), especially aquaporin 1 (AQP1) and aquaporin 4 (AQP4). AQPs are a family of transmembrane proteins involved in transport of water, glycerol, ions, and even CO 2 (15, 16). The 13-member family is ubiquitously expressed in almost all parts of the human body. Often more than one homolog is found to be present in any tissue or organ. In the brain AQP1, 3, 4, 5, 8, and 9 have been reported, with AQP1, 4, and 9 being expressed abundantly (17). The importance of AQP1 and AQP4 regulation in edema has been highlighted in several studies (18,19). AQP4 knockouts in mice showed increased protection against cytotoxic edema caused by water intoxication and permanent focal cerebral ischemia, whereas in conditions leading to vasogenic brain edema, it had a deleterious effect (18,19). s...

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Enhanced expression of aquaporin 4 in human brain with infarction

Cited by 115 publications

References 20 publications

The expression and the role of protease nexin-1 on brain edema after intracerebral hemorrhage

The expression and the role of protease nexin-1 on brain edema after intracerebral hemorrhage

Prestroke Proteomic Changes in Cerebral Microvessels in Stroke-Prone, Transgenic[hCETP]-Hyperlipidemic, Dahl Salt-Sensitive Hypertensive Rats

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

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