Sonic hedgehog enhances calcium oscillations in hippocampal astrocytes
| Autor: | Sen Takeda, Soo Hyun Jo, Satoshi Arai, Chihiro Adachi, Yusuke Arai, Takayuki Ishii, Tetsuya Kitaguchi, Takafumi Inoue, Naoto Kakinuma |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
animal structures Hippocampal formation Pertussis toxin Biochemistry Hippocampus 03 medical and health sciences Mice Calcium imaging Adenosine Triphosphate Neurobiology parasitic diseases Extracellular medicine Animals Hedgehog Proteins Calcium Signaling Sonic hedgehog Molecular Biology Cells Cultured Mice Inbred ICR 030102 biochemistry & molecular biology biology Chemistry Apyrase Cell Biology Smoothened Receptor Cell biology 030104 developmental biology medicine.anatomical_structure Astrocytes embryonic structures biology.protein Smoothened Carrier Proteins Astrocyte |
| Zdroj: | J Biol Chem |
| ISSN: | 1083-351X |
| Popis: | Sonic hedgehog (SHH) is important for organogenesis during development. Recent studies have indicated that SHH is also involved in the proliferation and transformation of astrocytes to the reactive phenotype. However, the mechanisms underlying these are unknown. Involvement of SHH signaling in calcium (Ca) signaling has not been extensively studied. Here, we report that SHH and Smoothened agonist (SAG), an activator of the signaling receptor Smoothened (SMO) in the SHH pathway, activate Ca oscillations in cultured murine hippocampal astrocytes. The response was rapid, on a minute time scale, indicating a noncanonical pathway activity. Pertussis toxin blocked the SAG effect, indicating an involvement of a G(i) coupled to SMO. Depletion of extracellular ATP by apyrase, an ATP-degrading enzyme, inhibited the SAG-mediated activation of Ca oscillations. These results indicate that SAG increases extracellular ATP levels by activating ATP release from astrocytes, resulting in Ca oscillation activation. We hypothesize that SHH activates SMO-coupled Gi in astrocytes, causing ATP release and activation of G(q/11)-coupled P2 receptors on the same cell or surrounding astrocytes. Transcription factor activities are often modulated by Ca patterns; therefore, SHH signaling may trigger changes in astrocytes by activating Ca oscillations. This enhancement of Ca oscillations by SHH signaling may occur in astrocytes in the brain in vivo because we also observed it in hippocampal brain slices. In summary, SHH and SAG enhance Ca oscillations in hippocampal astrocytes, G(i) mediates SAG-induced Ca oscillations downstream of SMO, and ATP-permeable channels may promote the ATP release that activates Ca oscillations in astrocytes. |
| Databáze: | OpenAIRE |
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