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Marine and Anthropogenic Bromopyrroles Alter Cellular Ca2+ Dynamics of Murine Cortical Neuronal Networks by Targeting the Ryanodine Receptor and Sarco/Endoplasmic Reticulum Ca2+-ATPase.
Zheng, Jing; Antrobus, Shane; Feng, Wei; Purdy, Trevor N; Moore, Bradley S; Pessah, Isaac N.
Afiliación
  • Zheng J; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States.
  • Antrobus S; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States.
  • Feng W; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616, United States.
  • Purdy TN; Center for Marine Biotechnology and Biomedicine, University of California, San Diego, California 92037, United States.
  • Moore BS; Scripps Institution of Oceanography, University of California, San Diego, California 92037, United States.
  • Pessah IN; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California 92037, United States.
Environ Sci Technol ; 55(23): 16023-16033, 2021 12 07.
Article en En | MEDLINE | ID: mdl-34788016
Bromopyrroles (BrPyr) are synthesized naturally by marine sponge symbionts and produced anthropogenically as byproducts of wastewater treatment. BrPyr interact with ryanodine receptors (RYRs) and sarco/endoplasmic reticulum (SR/ER) Ca2+-ATPase (SERCA). Influences of BrPyr on the neuronal network activity remain uncharted. BrPyr analogues with differing spectra of RYR/SERCA activities were tested using RYR-null or RYR1-expressing HEK293 and murine cortical neuronal/glial cocultures (NGCs) loaded with Fluo-4 to elucidate their mechanisms altering Ca2+ dynamics. The NGC electrical spike activity (ESA) was measured from NGCs plated on multielectrode arrays. Nanomolar tetrabromopyrrole (TBP, 1) potentiated caffeine-triggered Ca2+ release independent of extracellular [Ca2+] in RYR1-HEK293, whereas higher concentrations produce slow and sustained rise in cytoplasmic [Ca2+] independent of RYR1 expression. TBP, 2,3,5-tribromopyrrole (2), pyrrole (3), 2,3,4-tribromopyrrole (4), and ethyl 4-bromopyrrole-2-carboxylate (5) added acutely to NGC showed differential potency; rank order TBP (IC50 ≈ 220 nM) > 2 ≫ 5, whereas 3 and 4 were inactive at 10 µM. TBP >2 µM elicited sustained elevation of cytoplasmic [Ca2+] and loss of neuronal viability. TBP did not alter network ESA. BrPyr from marine and anthropogenic sources are ecological signaling molecules and emerging anthropogenic pollutants of concern to environmental and human health that potently alter ER Ca2+ dynamics and warrant further investigation in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenosina Trifosfatasas / Canal Liberador de Calcio Receptor de Rianodina Límite: Animals / Humans Idioma: En Revista: Environ Sci Technol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenosina Trifosfatasas / Canal Liberador de Calcio Receptor de Rianodina Límite: Animals / Humans Idioma: En Revista: Environ Sci Technol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos