Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues
S100B, a homodimeric Ca<sup>2+</sup>-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astr...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/23/16576 |
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| author | Marina C. Leite Fabiana Galland Maria Cristina Guerra Letícia Rodrigues Jéssica Taday Priscila T. Monteforte Hanko Hirata Carmem Gottfried Rosario Donato Soraya Smaili Carlos-Alberto Gonçalves |
| author_facet | Marina C. Leite Fabiana Galland Maria Cristina Guerra Letícia Rodrigues Jéssica Taday Priscila T. Monteforte Hanko Hirata Carmem Gottfried Rosario Donato Soraya Smaili Carlos-Alberto Gonçalves |
| author_sort | Marina C. Leite |
| collection | DOAJ |
| description | S100B, a homodimeric Ca<sup>2+</sup>-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astrocyte cultures and calcium measurements from real-time fluorescence microscopy to investigate the role of intracellular calcium in S100B secretion. In addition, the dimethyl sulfoxide (DMSO) effect on S100B was investigated in vitro and in vivo using Wistar rats. We found that DMSO, a widely used vehicle in biological assays, is a powerful S100B secretagogue, which caused a biphasic response of Ca<sup>2+</sup> mobilization. Our data show that astroglial S100B secretion is triggered by the increase in intracellular Ca<sup>2+</sup> and indicate that this increase is due to Ca<sup>2+</sup> mobilization from the endoplasmic reticulum. Also, blocking plasma membrane Ca<sup>2+</sup> channels involved in the Ca<sup>2+</sup> replenishment of internal stores decreased S100B secretion. The DMSO-induced S100B secretion was confirmed in vivo and in ex vivo hippocampal slices. Our data support a nonclassic vesicular export of S100B modulated by Ca<sup>2+</sup>, and the results might contribute to understanding the mechanism underlying the astroglial release of S100B. |
| first_indexed | 2024-03-09T01:50:34Z |
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| id | doaj.art-16c1a65c0f2c4bbc82c63b12ddf9db86 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:50:34Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-16c1a65c0f2c4bbc82c63b12ddf9db862023-12-08T15:16:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231657610.3390/ijms242316576Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as SecretagoguesMarina C. Leite0Fabiana Galland1Maria Cristina Guerra2Letícia Rodrigues3Jéssica Taday4Priscila T. Monteforte5Hanko Hirata6Carmem Gottfried7Rosario Donato8Soraya Smaili9Carlos-Alberto Gonçalves10Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre 90035-003, RS, BrazilCentro de Ciências e Qualidade dos Alimentos, Instituto de Tecnologia de Alimentos, Campinas 13070-178, SP, BrazilDepartamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre 90035-003, RS, BrazilDepartamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre 90035-003, RS, BrazilDepartamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre 90035-003, RS, BrazilDepartamento de Ciências Naturais, Universidade Federal de São João Del-Rei, São João Del Rei 36301-160, MG, BrazilDepartamento de Farmacologia, Universidade Federal de São Paulo, São Paulo 04044-020, SP, BrazilDepartamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre 90035-003, RS, BrazilInteruniversity Institute of Myology, 06132 Perugia, ItalyDepartamento de Farmacologia, Universidade Federal de São Paulo, São Paulo 04044-020, SP, BrazilDepartamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Ramiro Barcelos, 2600-Anexo, Porto Alegre 90035-003, RS, BrazilS100B, a homodimeric Ca<sup>2+</sup>-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astrocyte cultures and calcium measurements from real-time fluorescence microscopy to investigate the role of intracellular calcium in S100B secretion. In addition, the dimethyl sulfoxide (DMSO) effect on S100B was investigated in vitro and in vivo using Wistar rats. We found that DMSO, a widely used vehicle in biological assays, is a powerful S100B secretagogue, which caused a biphasic response of Ca<sup>2+</sup> mobilization. Our data show that astroglial S100B secretion is triggered by the increase in intracellular Ca<sup>2+</sup> and indicate that this increase is due to Ca<sup>2+</sup> mobilization from the endoplasmic reticulum. Also, blocking plasma membrane Ca<sup>2+</sup> channels involved in the Ca<sup>2+</sup> replenishment of internal stores decreased S100B secretion. The DMSO-induced S100B secretion was confirmed in vivo and in ex vivo hippocampal slices. Our data support a nonclassic vesicular export of S100B modulated by Ca<sup>2+</sup>, and the results might contribute to understanding the mechanism underlying the astroglial release of S100B.https://www.mdpi.com/1422-0067/24/23/16576S100B secretioncalcium signalingastrocytes |
| spellingShingle | Marina C. Leite Fabiana Galland Maria Cristina Guerra Letícia Rodrigues Jéssica Taday Priscila T. Monteforte Hanko Hirata Carmem Gottfried Rosario Donato Soraya Smaili Carlos-Alberto Gonçalves Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues International Journal of Molecular Sciences S100B secretion calcium signaling astrocytes |
| title | Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues |
| title_full | Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues |
| title_fullStr | Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues |
| title_full_unstemmed | Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues |
| title_short | Astroglial S100B Secretion Is Mediated by Ca<sup>2+</sup> Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues |
| title_sort | astroglial s100b secretion is mediated by ca sup 2 sup mobilization from endoplasmic reticulum a study using forskolin and dmso as secretagogues |
| topic | S100B secretion calcium signaling astrocytes |
| url | https://www.mdpi.com/1422-0067/24/23/16576 |
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