Transient activation of an adaptor protein, disabled-2, in rat spinal cord injury

Ahn, Meejung; Moon, Changjong; Park, Changnam; Kim, Jeong-Tae; Sim, Ki‐Bum; Shin, Taekyun

doi:10.1016/j.acthis.2014.11.001

Cited by 13 publications

(10 citation statements)

References 40 publications

(53 reference statements)

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“…To obtain reliable data associated with impact power, computerized data analyses have been applied using the New York University impact device [ 23 ], Ohio State University impact device [ 18 ], and MASCIS impactor [ 19 ]. Alternatively, for the present study, a clip compression technique was employed to induce SCI because there is a progressive improvement in BBB scores in rats following the use of this technique [ 2 21 24 ]. Additionally, the clip compression technique is an alternative choice for the induction of SCI in the absence of digital analysis systems, such as MASCIS [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

Kim

Ahn

et al. 2017

Anat Cell Biol

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Glycogen synthase kinase (GSK)-3β and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of GSK-3β, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative GSK-3β–associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of GSK-3β (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that GSK-3β becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of GSK-3β and the associated molecules Nrf-2 and HO-1.

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Section: Discussionmentioning

confidence: 99%

“…Spinal cord injury (SCI) is characterized by both mechanical and inflammatory response-induced damage [ 1 2 ]. The mechanical forces that impact the spinal cord at the time of injury may cause immediate tissue bursting [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

Kim

Ahn

et al. 2017

Anat Cell Biol

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“…In human K562 cells, Dab2 regulates internalization of TFR and uptake of TF 16 . Dab2 is also widely distributed in immune cells and in neuroglia 15 , although the functional link between Dab-2 and TFR in astrocytes has not been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

“…Cellular uptake of Fe 3+ requires internalization of TF-TFR complex 14 . An adaptor protein Disabled-2 (Dab2) plays an essential role in cell signalling, migration and development 15 . In mice the Dab2 has two isoforms of 96 and 67 kDa (p96 and p67 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Astrocytes express DMT1 and transferrin receptors, which transport iron thus activating Ca²⁺signalling: possible role in neuroprotection against iron overload?

Xia

Guan

et al. 2020

Preprint

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ABSTRACTIron is the fundamental element for numerous physiological functions. Reduced ferrous (Fe2+) and oxidized ferric (Fe3+) are the two ionized iron states in the living organisms. In the cell membrane, divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of Fe2+, whereas transferrin receptors (TFR) carry transferrin (TF)-bound Fe3+. In this study we performed, for the first time, detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca2+]i) in astrocytes. Using qPCR and immunocytochemistry we identified DMT1 and TFR in astrocytes in primary cultures, in acutely isolated astrocytes and in brain tissue preparations; in situ both DMT1 and TFR are concentrated in astroglial perivascular endfeet. Administration of Fe2+ or Fe3+ in low μM concentrations evoked Ca2+ signals in astrocytes in vitro and in vivo. Iron ions triggered increase in [Ca2+]i by acting through two distinct molecular cascades. Uptake of Fe2+ by DMT1 inhibited astroglial Na+-K+-ATPase (NKA), which led to an elevation in cytoplasmic Na+ concentration (as measured by SBFI probe), thus reversing Na+/Ca2+ exchanger (NCX) thereby generating Ca2+ influx. Uptake of Fe3+ by TF-TFR stimulated phospholipase C to produce inositol 1,4,5-trisphosphate (InsP3), thus trigering InsP3 receptor-mediated Ca2+ release from the endoplasmic reticulum. Iron-induced Ca2+ signals promote astroglial release of arachidonic acid and prostaglandin E2 cytokines by activating cytosolic phospholipase A2 (cPLA2) and NF-κB signalling cascade. In summary, these findings reveal new mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload, in response to which astrocytes actively accumulate excessive iron and activate neuroprotective pathways.

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Proper E‐cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer

Vázquez‐Carretero

García‐Miranda

Balda

et al. 2020

Journal Cellular Physiology

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We reported that Disabled-2 (Dab2) is located at the apical membrane in suckling rat intestine. Here, we discovered that, in colon of suckling and adult mouse and of adult human, Dab2 is only at lateral crypt cell membrane and colocalized with E-cadherin. Dab2 depletion in Caco-2 cells led to E-cadherin internalization indicating that its membrane location requires Dab2. In mice, we found that 3 days of dextran sulfate sodium-induced colitis increased Dab2/E-cadherin colocalization, which was decreased as colitis progressed to 6 and 9 days. In agreement, Dab2/ E-cadherin colocalization increased in human mild and severe ulcerative colitis and in polyps, being reduced in colon adenocarcinomas, which even showed epithelial Dab2 absence and E-cadherin delocalization. Epithelial Dab2 decrement preceded that of E-cadherin. We suggest that Dab2, by inhibiting E-cadherin internalization, stabilizes adherens junctions, and its absence from the epithelium may contribute to development of colon inflammation and cancer.

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Transient activation of an adaptor protein, disabled-2, in rat spinal cord injury

Cited by 13 publications

References 40 publications

Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

Astrocytes express DMT1 and transferrin receptors, which transport iron thus activating Ca²⁺signalling: possible role in neuroprotection against iron overload?

Proper E‐cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer

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Transient activation of an adaptor protein, disabled-2, in rat spinal cord injury

Cited by 13 publications

References 40 publications

Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1

Astrocytes express DMT1 and transferrin receptors, which transport iron thus activating Ca2+signalling: possible role in neuroprotection against iron overload?

Proper E‐cadherin membrane location in colon requires Dab2 and it modifies by inflammation and cancer

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Astrocytes express DMT1 and transferrin receptors, which transport iron thus activating Ca²⁺signalling: possible role in neuroprotection against iron overload?