Organohalogens naturally biosynthesized in marine environments and produced as disinfection byproducts alter sarco/endoplasmic reticulum ca2+ dynamics

TitleOrganohalogens naturally biosynthesized in marine environments and produced as disinfection byproducts alter sarco/endoplasmic reticulum ca2+ dynamics
Publication TypeJournal Article
Year of Publication2018
AuthorsZheng J, McKinnie S.MK, A. Gama E, Fengit W., Dong Y., Agarwal V., Fenical W, Kumar A., Cao Z.Y, Moore BS, Pessah I.N
JournalEnvironmental Science & Technology
Volume52
Pagination5469-5478
Date Published2018/05
Type of ArticleArticle
ISBN Number0013-936X
Accession NumberWOS:000431466500046
Keywordsbottle-nosed; channel complex; dolphins; Engineering; Environmental Sciences & Ecology; halogenated organic-compounds; mammalian-cell cytotoxicity; mass-spectrometry; polybrominated diphenyl ethers; polychlorinated-biphenyls; ryanodine receptor complex; sarcoplasmic-reticulum; skeletal-muscle
Abstract

Contemporary sources of organohalogens produced as disinfection byproducts (DBPs) are receiving considerable attention as emerging pollutants because of their abundance, persistence, and potential to structurally mimic natural organohalogens produced by bacteria that serve signaling or toxicological functions in marine environments. Here, we tested 34 organohalogens from anthropogenic and marine sources to identify compounds active toward ryanodine receptor (RyR1), known toxicological targets of non-dioxin like polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). [H-3]Ryanodine ([H-3]Ry) binding screening (<= 2 mu M) identified 10 highly active organohalogens. Further analysis indicated that 2,3-dibromoindole (14), tetrabromopyrrole (31), and 2,3,S-tribromopyrrole (34) at 10 mu M were the most efficacious at enhancing [H-3]Ry binding. Interestingly, these congeners also inhibited microsomal sarcoplasmic/endoplasmic reticulum (SR/ER) Ca2+ ATPase (SERCA1a). Dual SERCAla inhibition and RyR1 activation triggered Ca2+ efflux from microsomal vesicles with initial rates rank ordered 31 > 34 > 14. Hexabromobipyrroles (25) enhanced [H-3]Ry binding moderately with strong SERCAla inhibition, whereas pyrrole (24), 2,3,4-tribromopyrrole (26), and ethyl-4-bromopyrrole-2-carboxylate (27) were inactive. Of three PBDE derivatives of marine origin active in the [H-3]Ry assay, 4'-hydroxy-2,3',4,5',6-pentabromodiphenyl ether (18) was also a highly potent SERCAla inhibitor. Molecular targets of marine organohalogens that are also DBPs of emerging environmental concern are likely to contribute to their toxicity.

DOI10.1021/acs.est.8b00512
Short TitleEnviron. Sci. Technol.
Student Publication: 
No