Abstract

A strict coordination between pro- and antioxidative molecules is needed for normal animal physiology, although their exact function and dynamics during regeneration and development remains largely unknown. Via in vivo imaging, we were able to locate and discriminate between reactive oxygen species (ROS) in real-time during different physiological stages of the highly regenerative planarian Schmidtea mediterranea. All ROS signals were strong enough to overcome the detected autofluorescence. Combined with an in situ characterisation and quantification of the transcription of several antioxidant genes, our data showed that the planarian gut and epidermis have a well-equipped redox system. Pharmacological inhibition or RNA interference of either side of the redox balance resulted in alterations in the regeneration process, characterised by decreased blastema sizes and delayed neurodevelopment, thereby affecting tails more than heads. Focusing on glutathione, a central component in the redox balance, we found that it is highly present in planarians and that a significant reduction in glutathione content led to regenerative failure with tissue lesions, characterised by underlying stem cell alterations. This exploratory study indicates that ROS and antioxidants are tightly intertwined and should be studied as a whole to fully comprehend the function of the redox balance in animal physiology.

Highlights

  • IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

  • We found that regeneration is impaired upon interfering with reactive oxygen species (ROS) production and that the presence of hydrogen peroxide (H2 O2 )

  • In the last part of this study, we focused on glutathione and glutathione-related processes, with a specific focus on stem cell responses

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reactive oxygen species (ROS) fulfil an important role in animal physiology [1,2]. They are associated with oxidative stress and cell damage by altering DNA, RNA, proteins and other macromolecules [3]. During the last two decades, it became clear that ROS are regulating cell and tissue communication [1,4]. Serving as activators or signal transduction molecules in multiple pathways, they are involved in cell proliferation and survival, differentiation, metabolism and defence strategies [5]. A strong network of antioxidative (AOX) enzymes (e.g., catalase, superoxide dismutase) and metabolites, such as glutathione, keep the redox balance tightly regulated and controlled [6]

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