Blue light-emitting diode irradiation promotes transcription factor EB-mediated lysosome biogenesis and lysosomal cell death in murine photoreceptor-derived cells

Otsu, Wataru; Ishida, Kodai; Nakamura, Shinsuke; Shimazawa, Masamitsu; Tsusaki, Hideshi; Hara, Hideaki

doi:10.1016/j.bbrc.2020.03.118

Cited by 14 publications

(17 citation statements)

References 30 publications

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“…HCE-T cells cultured in 12-well plates (Corning Inc.) were harvested as described previously 39 . The lysates (2 µg of protein per lane) in RIPA buffer (Sigma-Aldrich, Cat# R0278) containing a protease inhibitor cocktail as well as phosphatase inhibitor cocktails 2 and 3 (Sigma-Aldrich) were subjected to SDS-PAGE on 5–20% gradient gels (SuperSep Ace, FUJIFILM-Wako) followed by immunoblotting.…”

Section: Methodsmentioning

confidence: 99%

Cigarette smoke extract and heated tobacco products promote ferritin cleavage and iron accumulation in human corneal epithelial cells

Otsu

Ishida

Chinen

et al. 2021

Sci Rep

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The cornea is directly exposed to cigarette smoke, and smoking is a risk factor for several corneal diseases including dry eye syndrome. Currently, heated tobacco products (HTPs) are widely used as substitutes for cigarette smoking around the world. In the present study, we investigated the molecular mechanism(s) leading to cellular injury induced by cigarette smoke extract (CSE) or HTPs. Exposure to CSE perturbed the formation of tight junctions, leading to an increase in cell volume, a decrease in transepithelial electrical resistance (TER) in the human corneal epithelial cell-transformed (HCE-T) cell line. Moreover, CSE exposure induced both lipid peroxidation and ferrous [Fe(II)] ion accumulation in autolysosomal compartments. Interestingly, a cleaved form of ferritin appeared when HCE-T cells were incubated with CSE. This aberrant ferritin processing was suppressed by treatment with autophagy inhibitors. Furthermore, the CSE-induced cell death was suppressed by either ferrostatin-1 or deferoxamine (DFO). CSE exposure also promoted the expression of cytokines whereas DFO treatment inhibited the CSE-induced expression of these cytokines. Exposure to HTPs also induced both HCE-T cell death and cleaved ferritin accumulation in a concentration- and time-dependent manner. These results indicated that CSE or HTPs activated the ferroptosis signaling pathway, which contributed to corneal epithelial cell injury.

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Section: Methodsmentioning

confidence: 99%

Cigarette smoke extract and heated tobacco products promote ferritin cleavage and iron accumulation in human corneal epithelial cells

Otsu

Ishida

Chinen

et al. 2021

Sci Rep

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“…Quantitative RT-PCR Quantitative reverse transcriptasepolymerase chain reaction (RT-PCR) was performed, as described previously. 20) In brief, total RNA was purified from NSC-34 cells, grown in a 12-well plate (Corning), using NucleoSpin RNA (Takara Bio), and subjected to reverse transcription to generate a cDNA library, using Prime-Script RT reagent Kit (Takara Bio). Quantitative RT-PCR was performed on a Thermal Cycler Dice Real-Time System III (Takara Bio), using TB Green Premix Ex Taq II (Takara Bio).…”

Section: Methodsmentioning

confidence: 99%

Survival Motor Neuron Protein Modulates Lysosomal Function Through the Expression of Transcription Factor EB in Motoneurons

et al. 2020

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Spinal muscular atrophy (SMA) is a progressive neuromuscular disease, associated with motoneuron loss and muscle wasting. Numerous SMA-causative mutations have been reported in survival motor neuron (SMN) gene(s); however, the pathogenic mechanism underlying SMA remains unclear. In the present study, we showed that SMN modulates the expression of transcription factor EB (TFEB), a master regulator of lysosomal genes that plays a key role in lysosome function, autophagy, and the mammalian target of rapamycin (mTOR) signaling pathway. The transfection of small interfering RNA (siRNA) targeting SMN caused a reduction in TFEB expression in the motoneuron-like NSC-34 cell line. In differentiated NSC-34 cells, either SMN or TFEB knockdown resulted in reduced lysosomes at neurites and the atypical accumulation of swollen and enlarged lysosomes in cell bodies. SMN knockdown caused the reduced expression of lysosome-related genes, resulting in the decline of lysosomal degradation and increased autophagic flux. These SMN-depletion-induced aberrations in lysosomes and autophagy could be rescued by the exogenous expression of TFEB. Furthermore, SMN depletion in NSC-34 cells resulted in the decreased phosphorylation of mTOR and its downstream signals. Finally, SMA transgenic mice exhibited reduced TFEB and lysosomal protein expression and the inactivation of mTOR signaling in the lumbar spinal cord at postnatal day 11, compared with their counterparts. These findings indicated that SMN regulates lysosomal gene expression and functions by altering TFEB expression in motoneurons. The targeting of lysosomes might represent a new strategy for the treatment of SMA.

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“…Lysosomes are one of the most important calcium storage of cells, with a concentration ranging from 0.2 to 0.6 mM, compared to 0.1 nM in the cytoplasm (Bagur & Hajnoczky, 2017; Pihan et al, 2022). Calcium signaling regulates important functions of lysosomes, such as biogenesis, exocytosis, and lysosomal fusion with other vesicles (Otsu et al, 2020; Siow et al, 2022). However, as an important intracellular signal, most studies on calcium are limited to the endoplasmic reticulum and mitochondria.…”

Section: Intrinsic Mechanisms Of Lmp For Cancer Therapymentioning

confidence: 99%

Magnetic modulation of lysosomes for cancer therapy

Li,

Lv,

et al. 2024

WIREs Nanomed Nanobiotechnol

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Lysosomes play a central role in biochemical signal transduction and oxidative stress in cells. Inducing lysosome membrane penetration (LMP) to cause lysosomal‐dependent cell death (LCD) in tumor cells is an effective strategy for cancer therapy. Chemical drugs can destroy the stability of lysosomes by neutralizing protons within the lysosomes or enhancing the fragility of the lysosomal membranes. However, there remain several unsolved problems of traditional drugs in LMP induction due to insufficient lysosomal targeting, fast metabolism, and toxicity in normal cells. With the development of nanotechnology, magnetic nanoparticles have been demonstrated to target lysosomes naturally, providing a versatile tool for lysosomal modulation. Combined with excellent tissue penetration and spatiotemporal manipulability of magnetic fields, magnetic modulation of lysosomes progresses rapidly in inducing LMP and LCD for cancer therapy. This review comprehensively discussed the strategies of magnetic modulation of lysosomes for cancer therapy. The intrinsic mechanisms of LMP‐induced LCD were first introduced. Then, the modulation of lysosomes by diverse physical outputs of magnetic fields was emphatically discussed. Looking forward, this review will shed the light on the prospect of magnetic modulation of lysosomes, inspiring future research of magnetic modulation strategy in cancer therapy.This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Blue light-emitting diode irradiation promotes transcription factor EB-mediated lysosome biogenesis and lysosomal cell death in murine photoreceptor-derived cells

Cited by 14 publications

References 30 publications

Cigarette smoke extract and heated tobacco products promote ferritin cleavage and iron accumulation in human corneal epithelial cells

Cigarette smoke extract and heated tobacco products promote ferritin cleavage and iron accumulation in human corneal epithelial cells

Survival Motor Neuron Protein Modulates Lysosomal Function Through the Expression of Transcription Factor EB in Motoneurons

Magnetic modulation of lysosomes for cancer therapy

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