Light-controlled inhibition of malignant glioma by opsin gene transfer

Yang, Fan; Tu, Jing; Jq, Pan; Hl, Luo; Yh, Liu; Wan, Jianxin; Zhang, J; Pf, Wei; Jiang, Tao; Chen, Y-H.; Wang, Li Ping

doi:10.1038/cddis.2013.425

Cited by 21 publications

(23 citation statements)

References 44 publications

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“…; Aprea & Calegari, ; Levin, , ; Pai & Levin, ; Yang et al . ; Wang et al . ), we believe that application of optogenetics to non‐neural, non‐excitable cells will become a transformative tool for understanding the role of biophysical signals in numerous birth defects.…”

Section: Discussionmentioning

confidence: 99%

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

Adams

Uzel

Akagi

et al. 2016

The Journal of Physiology

127

140

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Key pointsr Xenopus laevis craniofacial development is a good system for the study of Andersen-Tawil Syndrome (ATS)-associated craniofacial anomalies (CFAs) because (1) Kcnj2 is expressed in the nascent face; (2) molecular-genetic and biophysical techniques are available for the study of ion-dependent signalling during craniofacial morphogenesis; (3) as in humans, expression of variant Kcnj2 forms in embryos causes a muscle phenotype; and (4) variant forms of Kcnj2 found in human patients, when injected into frog embryos, cause CFAs in the same cell lineages. r Expression of other potassium channels and two different light-activated channels, all of which have an effect on V mem , causes CFAs like those induced by injection of Kcnj2 variants. In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an inactive Cl − channel, do not cause CFAs, demonstrating that correct craniofacial development depends on a pattern of bioelectric states, not on ion-or channel-specific signalling.r Using optogenetics to control both the location and the timing of ion flux in developing embryos, we show that affecting V mem of the ectoderm and no other cell layers is sufficient to cause CFAs, but only during early neurula stages. Changes in V mem induced late in neurulation do not affect craniofacial development.r We interpret these data as strong evidence, consistent with our hypothesis, that ATS-associated CFAs are caused by the effect of variant Kcnj2 on the V mem of ectodermal cells of the developing face. We predict that the critical time is early during neurulation, and the critical cells are the ectodermal cranial neural crest and placode lineages. This points to the potential utility of extant, ion flux-modifying drugs as treatments to prevent CFAs associated with channelopathies such as ATS.Abstract Variants in potassium channel KCNJ2 cause Andersen-Tawil Syndrome (ATS); the induced craniofacial anomalies (CFAs) are entirely unexplained. We show that KCNJ2 is expressed in Xenopus and mouse during the earliest stages of craniofacial development. resting potentials using other ion translocators, we show that a change in ectodermal voltage, not tied to a specific protein or ion, is sufficient to cause CFAs. By adapting optogenetics for use in non-neural cells in embryos, we show that developmentally patterned K + flux is required for correct regionalization of the resting potentials and for establishment of endogenous early gene expression domains in the anterior ectoderm, and that variants in KCNJ2 disrupt this regionalization, leading to the CFAs seen in ATS patients.

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Section: Discussionmentioning

confidence: 99%

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

Adams

Uzel

Akagi

et al. 2016

The Journal of Physiology

127

140

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“…A wide variety of opsins exist in vertebrates as photoreceptors, and each has an optimal wavelength. The first report of the relationship between opsins and tumor suppression was reported by Yang et al, who showed that opsin gene transfers with blue LED irradiation inhibited the growth of malignant glioma. In the opsin family, Opn3 is known as a blue light receptor and is widely expressed in non‐visual cells.…”

Section: Discussionmentioning

confidence: 99%

Blue light‐emitting diodes induce autophagy in colon cancer cells by Opsin 3

Yoshimoto

Morine

Takasu

et al. 2018

Annals of Gastroent Surgery

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BackgroundLight emitting‐diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro.MethodsHuman colon cancer cells (HT‐29 or HCT‐116) were seeded onto laboratory dishes and irradiated with 465‐nm LED at 30 mW/cm2 for 30 minutes. Cell Counting Kit‐8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription‐polymerase chain reaction (RT‐PCR), respectively. Autophagy and expression of LC‐3 and beclin‐1 were also evaluated by autophagy assays, RT‐PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the Gi/o G‐protein inhibitor NF023 in these assays.ResultsViability of HT‐29 and HCT‐116 cells was lower in 465‐nm LED‐irradiated cultures than in control cultures. LC‐3 and beclin‐1 expressions were significantly higher in LED‐irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC‐3 and beclin‐1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment.ConclusionBlue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.

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“…In addition to remote control of excitable cells, optogenetic techniques have been used to induce and study cell death. For instance, Yang et al showed that an optogenetic approach can induce apoptotic cell death in human glioma cells via depolarization of cell membrane potential and influx of Ca 2+ (26). In another study, Hill et al reported a two-photon chemical apoptotic targeted ablation technique (27).…”

Section: Introductionmentioning

confidence: 99%

Precisely control mitochondria with light to manipulate cell fate decision

Erñst

Yun

et al. 2018

Preprint

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Mitochondrial dysfunction has been implicated in many pathological conditions and diseases. The normal functioning of mitochondria relies on maintaining the inner mitochondrial membrane (IMM) potential (a.k.a. ΔΨ m ) that is essential for ATP synthesis, Ca 2+ homeostasis, redox balance and regulation of other key signaling pathways such as mitophagy and apoptosis.However, the detailed mechanisms by which ΔΨ m regulates cellular function remain incompletely understood, partially due to difficulty of manipulating ΔΨ m with spatiotemporal resolution, reversibility, or cell type specificity. To address this need, we have developed a nextgeneration optogenetic-based technique for controllable mitochondrial depolarization with light. We demonstrate successful targeting of the heterologous Channelrhodopsin-2 (ChR2) fusion protein to the IMM and formation of functional cationic channels capable of light-induced selective ΔΨ m depolarization and mitochondrial autophagy. Importantly, we for the first time show that optogenetic-mediated mitochondrial depolarization can be well-controlled to differentially influence the fate of cells expressing mitochondrial ChR2: while sustained moderate light illumination induces substantial apoptotic cell death, transient mild light illumination elicits cytoprotection via mitochondrial preconditioning. Finally, we show that Parkin overexpression exacerbates, instead of ameliorating, mitochondrial depolarization-mediated cell death in HeLa cells. In summary, we provide evidence that the described mitochondrial-targeted optogenetics may have a broad application for studying the role of mitochondria in regulating cell function and fate decision.

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Light-controlled inhibition of malignant glioma by opsin gene transfer

Cited by 21 publications

References 44 publications

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

Blue light‐emitting diodes induce autophagy in colon cancer cells by Opsin 3

Precisely control mitochondria with light to manipulate cell fate decision

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