Lipid Oxidation Induced by RF Waves and Mediated by Ferritin Iron Causes Activation of Ferritin-Tagged Ion Channels

Hernández-Morales, Miriam; Shang, Trisha; Chen, Jingjia; Han, V. K. M.

doi:10.1016/j.celrep.2020.02.070

Cited by 31 publications

(69 citation statements)

References 44 publications

(87 reference statements)

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“…This ROS-based mechanism is supported by the recent work of Hernández-Morales et al on the chemical activation of ferritin-based magnetogenetic platforms exposed to RF-AMF 54 . Activation of various TRP channels conjugated to ferritin by the kininogen-1 domain 5, a known ferritin-binding domain, was shown to increase Ca 2+ influx upon exposure to 12 μT, 180 MHz AMF.…”

Section: Discussionmentioning

confidence: 61%

“…Activation of various TRP channels conjugated to ferritin by the kininogen-1 domain 5, a known ferritin-binding domain, was shown to increase Ca 2+ influx upon exposure to 12 μT, 180 MHz AMF. They demonstrated that the RF-AMF increased the labile iron pool resulting in generation of ROS that subsequently increased the oxidized lipid content in the cell membrane 54 . These results support the proposed chemical mechanism that ROS generated by ferritin gates TRPV1 specifically when exposed to RF-AMFs.…”

Section: Discussionmentioning

confidence: 99%

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Uncovering a possible role of reactive oxygen species in magnetogenetics

Brier

Mundell

et al. 2020

Sci Rep

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Recent reports have shown that intracellular, (super)paramagnetic ferritin nanoparticles can gate TRPV1, a non-selective cation channel, in a magnetic field. Here, we report the effects of differing field strength and frequency as well as chemical inhibitors on channel gating using a Ca 2+-sensitive promoter to express a secreted embryonic alkaline phosphatase (SEAP) reporter. Exposure of TRPV1ferritin-expressing HEK-293T cells at 30 °C to an alternating magnetic field of 501 kHz and 27.1 mT significantly increased SEAP secretion by ~ 82% relative to control cells, with lesser effects at other field strengths and frequencies. Between 30-32 °C, SEAP production was strongly potentiated 3.3-fold by the addition of the TRPV1 agonist capsaicin. This potentiation was eliminated by the competitive antagonist AMG-21629, the NADPH oxidase assembly inhibitor apocynin, and the reactive oxygen species (RoS) scavenger N-acetylcysteine, suggesting that ROS contributes to magnetogenetic TRPV1 activation. These results provide a rational basis to address the heretofore unknown mechanism of magnetogenetics. New approaches have been advanced for controlling signal transduction 1 , cell activity, and protein expression 2 with temporal precision, contributing to advances in on-demand biomanufacturing of protein biologics 3 , developing new tools for drug discovery 4 , in vitro expansion and differentiation of stem cells for regenerative medicine 5 , and regulating the activity of neurons and other cell types in vivo 5. One example is optogenetics, which uses precise wavelengths of light to stimulate light sensitive channels 6,7. Alternatively, gold nanorods (AuNRs) can be actuated by near-infrared (NIR) wavelengths to confer light-sensitivity to light-insensitive, heat-sensitive targets. Specifically, antibody-coated AuNRs targeted to transient receptor potential (TRP) vanilloid 1 (TRPV1) cation channels and integrins generated plasmonic heating when stimulated with select wavelengths of NIR light and gated Ca 2+ flux into cells to control cellular functions 8. In each optical technique, the low penetration depth of visible and NIR light into cellular systems limits application either in vitro or in vivo 9. Another example is chemogenetics, in which drug ligands can gate mutated ion channels 10 or G-protein coupled receptors 11. Chemogenetics does not require an implant but is limited by a slow onset of action that is dictated by the pharmacokinetics of the drug actuator in vivo and the addition of a chemical inducer to in vitro cell-based reactors 12. Still other approaches for activating signal transduction have been developed including the use of size-controlled microbubbles targeted to Piezo1 ion channels to gate Ca 2+ flux by ultrasound stimulation 13 and magnetic activation of engineered ion channels 14-18. The use of magnetic fields to gate TRPV1 and related ion channels has been shown in multiple studies. Pralle and co-workers used megahertz radio frequency (RF) alternating magnetic fields (AMFs) to gate TRPV1 when external ...

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Uncovering a possible role of reactive oxygen species in magnetogenetics

Brier

Mundell

et al. 2020

Sci Rep

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“…To evaluate the influence of the time delays between seeding, transfection, and functional expression of TRPV4 FeRIC , we examined three different timing protocols (Fig. 1A) that correspond to those reported for magnetic control of ferritin-tagged TRPV (Hernández-Morales et al, 2020;Hutson et al, 2017;Stanley et al, 2016;Wheeler et al, 2016). As previously reported, RF stimulation does not change the cytosolic Ca 2+ levels in N2a cells expressing only GCaMP6.…”

Section: Results Experimental Factors Affect the Rf Efficacy To Inducmentioning

confidence: 89%

“…A crucial component of most of the magnetogenetics approaches is the TRPV channels (Chen et al, 2015;Duret et al, 2019;Hernández-Morales et al, 2020;Huang et al, 2010;Hutson et al, 2017Hutson et al, , 2017Stanley et al, 2015Stanley et al, , 2016Wheeler et al, 2016). Notably, the functional expression of TRPV is regulated by activity-dependent mechanisms, resulting in dynamic trafficking between the cell membrane and the cytosolic vesicle pool.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of TRPV4 FeRIC with RF at kHz and MHz frequencies. It has been reported that RF waves at high kHz (Stanley et al, 2015(Stanley et al, , 2016 or MHz (Hernández-Morales et al, 2020;Hutson et al, 2017) frequencies activate ferritin-tagged TRPV. Before examining if the RF-induced activation of TRPV4 FeRIC depends on RF frequency, we first estimated the distribution of the electric (E) and magnetic (B) fields applied to the cells to rule out the potential contribution of the electrical field to the RF-induced Ca 2+ responses in cells expressing TRPV4 FeRIC .…”

Section: D E S3)mentioning

confidence: 99%

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Evaluating Methods and Protocols of Ferritin-Based Magnetogenetics

Hernández-Morales

Han

Kramer³

2020

Preprint

Self Cite

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FeRIC (Ferritin iron Redistribution to Ion Channels) is a magnetogenetic technique that uses radiofrequency (RF) waves to activate the transient receptor potential channels, such as TRPV1 and TRPV4, coupled to cellular ferritins. In cells expressing ferritin-tagged TRPV, RF stimulation increases the cytosolic Ca2+ levels via a biochemical pathway. The interaction between RF and ferritin increases the free cytosolic iron level that in turn, triggers chemical reactions producing reactive oxygen species and oxidized lipids that activate the ferritin-tagged TRPV. In this pathway, it is expected that experimental factors that disturb the ferritin expression, the ferritin iron load, the TRPV functional expression, or the cellular redox state will impact the RF efficacy to activate ferritin-tagged TRPV. Here, three in vitro protocols were compared for using FeRIC to remotely activate ferritin-tagged TRPV. Further, several experimental factors were examined that either enhance or abolish the RF control of ferritin-tagged TRPV. The findings may help establish reproducible magnetogenetic experimental protocols.

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NIR‐Actuated Remote Activation of Ferroptosis in Target Tumor Cells through a Photothermally Responsive Iron‐Chelated Biopolymer Nanoplatform

Xue

Liu

et al. 2021

Angewandte Chemie

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Ferroptosis is anew form of regulated cell death that shows promise for tumor treatment. Most current ferroptosis tumor therapies are based on the intrinsic pathological features of the malignancies,and it would be of clinical significance to develop ferroptosis-inducing strategies with improved tumor specificity and modulability.Here we report ap olydopaminebased nanoplatform (Fe II PDA@LAP-PEG-cRGD) for the efficient loading of Fe 2+ and b-lapachone (LAP), which could readily initiate ferroptosis in tumor cells upon treatment with near-infrared light. PDAn anostructures could generate mild hyperthermia under NIR irritation and trigger the release of the ferroptosis-inducing Fe 2+ ions.T he NIR-actuated photothermal effect would also activate cellular heat shock response and upregulate the downstream NQO1 via HSP70/NQO1 axis to facilitate bioreduction of the concurrently released b-lapachone and enhance intracellular H 2 O 2 formation to promote the Fe 2+-mediated lipid peroxidation.

show abstract

Lipid Oxidation Induced by RF Waves and Mediated by Ferritin Iron Causes Activation of Ferritin-Tagged Ion Channels

Cited by 31 publications

References 44 publications

Uncovering a possible role of reactive oxygen species in magnetogenetics

Uncovering a possible role of reactive oxygen species in magnetogenetics

Evaluating Methods and Protocols of Ferritin-Based Magnetogenetics

NIR‐Actuated Remote Activation of Ferroptosis in Target Tumor Cells through a Photothermally Responsive Iron‐Chelated Biopolymer Nanoplatform

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