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Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis.

ABSTRACT: Exposures to a hypomagnetic field can affect biological processes. Recently, it has been observed that hypomagnetic field exposure can adversely affect adult hippocampal neurogenesis and hippocampus-dependent cognition in mice. In the same study, the role of reactive oxygen species (ROS) in hypomagnetic field effects has been demonstrated. However, the mechanistic reasons behind this effect are not clear. This study proposes a radical pair mechanism based on a flavin-superoxide radical pair to explain the modulation of ROS production and the attenuation of adult hippocampal neurogenesis in a hypomagnetic field. The results of our calculations favor a singlet-born radical pair over a triplet-born radical pair. Our model predicts hypomagnetic field effects on the triplet/singlet yield of comparable strength as the effects observed in experimental studies on adult hippocampal neurogenesis. Our predictions are in qualitative agreement with experimental results on superoxide concentration and other observed ROS effects. We also predict the effects of applied magnetic fields and oxygen isotopic substitution on adult hippocampal neurogenesis.

SUBMITTER: Rishabh R

PROVIDER: S-EPMC9197044 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis.

Rishabh Rishabh R Zadeh-Haghighi Hadi H Salahub Dennis D Simon Christoph C

PLoS computational biology 20220602 6

Exposures to a hypomagnetic field can affect biological processes. Recently, it has been observed that hypomagnetic field exposure can adversely affect adult hippocampal neurogenesis and hippocampus-dependent cognition in mice. In the same study, the role of reactive oxygen species (ROS) in hypomagnetic field effects has been demonstrated. However, the mechanistic reasons behind this effect are not clear. This study proposes a radical pair mechanism based on a flavin-superoxide radical pair to e ...[more]

PMID: 35653379

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Project description:Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN-MES transition. This 'reprogramming' of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.

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Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis.

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Radical pairs may explain reactive oxygen species-mediated effects of hypomagnetic field on neurogenesis.

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