Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups
Brevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. Lower doses, in contrast, have been shown to elicit neuroregeneration. Brevetoxins have thus been prop...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/20/4/233 |
| _version_ | 1797434431811616768 |
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| author | Jennifer R. McCall Kathryn T. Sausman Devon M. Keeler Ariel P. Brown Stephanie L. Turrise |
| author_facet | Jennifer R. McCall Kathryn T. Sausman Devon M. Keeler Ariel P. Brown Stephanie L. Turrise |
| author_sort | Jennifer R. McCall |
| collection | DOAJ |
| description | Brevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. Lower doses, in contrast, have been shown to elicit neuroregeneration. Brevetoxins have thus been proposed as a novel treatment for patients after stroke, when neuron regrowth and repair is critical to recovery. However, findings from environmental exposures indicate that brevetoxins may cause inflammation, thus, there is concern for brevetoxins as a stroke therapy given the potential for neuroinflammation. In this study, we examined the inflammatory properties of several brevetoxin analogs, including those that do and do not bind strongly to VGSCs, as binding has classically indicated toxicity. We found that several analogs are toxic to monocytes, while others are not, and the degree of toxicity is not directly related to VGSC binding. Rather, results indicate that brevetoxins containing aldehyde groups were more likely to cause immunotoxicity, regardless of binding affinity to the VGSC. Our results demonstrate that different brevetoxin family members can elicit a spectrum of apoptosis and necrosis by multiple possible mechanisms of action in monocytes. As such, care should be taken in treating “brevetoxins” as a uniform group, particularly in stroke therapy research. |
| first_indexed | 2024-03-09T10:32:08Z |
| format | Article |
| id | doaj.art-860f89dbdf6c4f3ab93562b339b531b0 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T10:32:08Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-860f89dbdf6c4f3ab93562b339b531b02023-12-01T21:10:52ZengMDPI AGMarine Drugs1660-33972022-03-0120423310.3390/md20040233Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive GroupsJennifer R. McCall0Kathryn T. Sausman1Devon M. Keeler2Ariel P. Brown3Stephanie L. Turrise4School of Nursing, College of Health and Human Services, University of North Carolina Wilmington, Wilmington, NC 28403, USASchool of Nursing, College of Health and Human Services, University of North Carolina Wilmington, Wilmington, NC 28403, USASeaTox Research Inc., Wilmington, NC 28409, USASchool of Nursing, College of Health and Human Services, University of North Carolina Wilmington, Wilmington, NC 28403, USASchool of Nursing, College of Health and Human Services, University of North Carolina Wilmington, Wilmington, NC 28403, USABrevetoxins are a suite of marine neurotoxins that activate voltage-gated sodium channels (VGSCs) in cell membranes, with toxicity occurring from persistent activation of the channel at high doses. Lower doses, in contrast, have been shown to elicit neuroregeneration. Brevetoxins have thus been proposed as a novel treatment for patients after stroke, when neuron regrowth and repair is critical to recovery. However, findings from environmental exposures indicate that brevetoxins may cause inflammation, thus, there is concern for brevetoxins as a stroke therapy given the potential for neuroinflammation. In this study, we examined the inflammatory properties of several brevetoxin analogs, including those that do and do not bind strongly to VGSCs, as binding has classically indicated toxicity. We found that several analogs are toxic to monocytes, while others are not, and the degree of toxicity is not directly related to VGSC binding. Rather, results indicate that brevetoxins containing aldehyde groups were more likely to cause immunotoxicity, regardless of binding affinity to the VGSC. Our results demonstrate that different brevetoxin family members can elicit a spectrum of apoptosis and necrosis by multiple possible mechanisms of action in monocytes. As such, care should be taken in treating “brevetoxins” as a uniform group, particularly in stroke therapy research.https://www.mdpi.com/1660-3397/20/4/233brevetoxininflammationmonocyteT cellcytotoxicityapoptosis |
| spellingShingle | Jennifer R. McCall Kathryn T. Sausman Devon M. Keeler Ariel P. Brown Stephanie L. Turrise Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups Marine Drugs brevetoxin inflammation monocyte T cell cytotoxicity apoptosis |
| title | Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups |
| title_full | Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups |
| title_fullStr | Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups |
| title_full_unstemmed | Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups |
| title_short | Immune Modulating Brevetoxins: Monocyte Cytotoxicity, Apoptosis, and Activation of M1/M2 Response Elements Is Dependent on Reactive Groups |
| title_sort | immune modulating brevetoxins monocyte cytotoxicity apoptosis and activation of m1 m2 response elements is dependent on reactive groups |
| topic | brevetoxin inflammation monocyte T cell cytotoxicity apoptosis |
| url | https://www.mdpi.com/1660-3397/20/4/233 |
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