Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid.

Heidi Wichmann,Meinhard Simon,Thorsten Brinkhoff,Christiane Richter-Landsberg

doi:10.3390/md14050089

Heidi Wichmann, Meinhard Simon + Show 2 more

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https://doi.org/10.3390/md14050089

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Journal: Marine Drugs	Publication Date: May 6, 2016
Citations: 12	License type: CC BY 4.0

Affiliation: Carl von Ossietzky University of Oldenburg

Abstract

The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.

Highlights

Marine organisms produce a high diversity of structurally unique natural products with a broad spectrum of biological activities, including anti-cancer or antimicrobial effects, and some compounds even show a promising potential of neurotrophic or neuroprotective activity [1,2,3,4]
As we have shown before, tropodithietic acid (TDA) induced cytotoxic responses in both cell lines, caused the breakdown of the mitochondrial membrane potential, the activation of extracellular signal-regulated kinases extracellular signal-regulated kinases 1/2 (ERK1/2) and the upregulation of the small heat shock protein HSP32, which has been linked to the induction of oxidative stress [32,33]
When it is released into the environment, DMSP is rapidly degraded by marine bacteria, such as roseobacters [8]

Summary

Introduction

Marine organisms produce a high diversity of structurally unique natural products with a broad spectrum of biological activities, including anti-cancer or antimicrobial effects, and some compounds even show a promising potential of neurotrophic or neuroprotective activity [1,2,3,4]. Natural products of marine algae, derived from the algae themselves or their bacterial associates, are a focal point in drug discovery programs due to their various biological activities [5,6]. In addition to its role in natural biogeochemical processes, DMSP has been found as a promising bioactive compound for biomedical research.

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