Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells

Tabuchi, Yoshiaki; Yunoki, Tatsuya; Hoshi, Nobuhiko; Suzuki, Nobuo; Kondo, Takashi

doi:10.3390/ijms15058959

Cited by 19 publications

(22 citation statements)

References 57 publications

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“…The decrease of mitochondrial membrane potential (MMP) is a key indicator of early apoptosis, which can cause the release of apoptotic factors and activate the downstream apoptotic pathways . Consequently, the MMP was determined by JC‐1, a fluorescence probe, which can selectively enter into mitochondria and reversibly change color from red (the aggregate form) to green (the monomeric form) when mitochondrial membrane potential declines . As shown in Figure.…”

Section: Resultsmentioning

confidence: 99%

Rh(III)‐Catalyzed Redox‐Neutral [4+2] Annulation for Direct Assembly of 3‐Acyl Isoquinolin‐1(2H)‐ones as Potent Antitumor Agents

Bian

et al. 2019

ChemPlusChem

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By virtue of an efficient rhodium(III)‐catalyzed redox‐neutral C−H activation/ring‐opening of a strained ring/[4+2] annulation cascade of N‐methoxybenzamides with propargyl cycloalkanols, diverse 3‐acyl isoquinolin‐1(2H)‐ones were directly obtained in good yields and with excellent functional group compatibility. Additionally, their antitumor activities against various human cancer cells including HepG2, A549, MCF‐7 and SH‐SY5Y were evaluated and the action mechanism of the selected compound was also investigated in vitro. The results revealed that these products possessed a potent efficacy, by inhibiting proliferation and inducing apoptosis in a time‐dependent and dose‐dependent manner, suggesting that such compounds can serve as promising candidates for anti lung cancer drug discovery.

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Section: Resultsmentioning

confidence: 99%

Rh(III)‐Catalyzed Redox‐Neutral [4+2] Annulation for Direct Assembly of 3‐Acyl Isoquinolin‐1(2H)‐ones as Potent Antitumor Agents

Bian

et al. 2019

ChemPlusChem

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“…Oxidative stress plays a vital role in uoride-induced toxicities [35,36], and the involvement of this stress response in uoride-induced autophagy remains speculative. In the present study, levels of ATG5 and Beclin1, which re ect the autophagy status [37], were obviously decreased in cementoblasts and periodontal tissues following NaF exposure.…”

Section: Discussionmentioning

confidence: 99%

Oral toxicity to high level sodium fluoride causes impairment of autophagy

Oka

Zhang

et al. 2020

Preprint

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Background: Gingival recession and concomitant alveolar bone resorption are hallmarks of periodontal diseases and excessive fluoride intake has some deleterious effects on teeth, bone and soft tissues. Autophagy is a highly conserved intracellular digestion process that degrades damaged proteins and organelles but the biological roles of autophagy in pathological aspects of oral tissues remain largely unknown. We sought to elucidate the function of autophagy, especially its interplay with apoptosis and oxidative stress, in the oral toxicity induced by exposure to 5 mM sodium fluoride (NaF). Methods: HCEM2 cementoblast cells in culture were exposed to 5 mM NaF for 5 min, after which cell viability and cell apoptosis were assessed using the MTS assay and an Annexin V-FITC/PI apoptosis detection kit, respectively. Real-time quantitative RT-PCR and Western blotting were performed to characterize the mRNA and protein expression levels of markers for autophagy, apoptosis, and oxidative stress. C57BL/6 mice were exposed to 5 mM NaF in their drinking water from 12 to 58 weeks. Micro-computed tomography was used to measure changes in their alveolar bone while immunohistochemistry and immunofluorescence staining was used to evaluate protein expression levels of autophagy, apoptosis, and oxidative stress markers.Results: Cementoblasts exposed to 5 mM NaF had decreased levels of autophagy, as shown by reduced expression levels of ATG5, Beclin1 and LC3-II, elicited excessive apoptosis, which in turn induced oxidative stress and inflammation, as manifested by elevated levels of Bax, cleaved caspase-3, SOD1 and phospho NF-κB. Consistently, the in vivo results verified the findings of the in vitro study and treatment of mice with 5 mM NaF resulted in histological abnormalities in periodontal tissues, induced excessive oxidative stress and apoptosis, and reduced autophagy. These results correlated with the immunofluorescence observations, thus confirming the pivotal role of autophagic flux dysfunction in 5 mM NaF-induced cell death. Micro-computed tomography analysis demonstrated that 5 mM NaF caused a decrease in bone areas of mice compared with controls. Exposure to 5 mM NaF induced RANKL (receptor activator of nuclear factor κB ligand) and cathepsin K expression in periodontal tissues, while ATG5 and Beclin1 expression was abrogated by 5 mM NaF.Conclusion: Taken together, our findings suggest that 5 mM NaF elicits oral toxicity that contributes to excessive apoptosis, oxidative stress, and defective autophagy, which aggravates periodontal tissue damage.

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“…The data were further analyzed using the GeneSpring ® GX software (Agilent Technologies, Inc.) to extract the significant genes. For gene ontology analysis, including that pertaining to biological processes, cellular components, molecular functions, and gene networks, the data obtained were analyzed using Ingenuity ® Pathway Analysis tools (Ingenuity Systems, Inc., Mountain View, CA, USA) (12,13).…”

Section: Methodsmentioning

confidence: 99%

Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling

et al. 2018

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Basal cell carcinoma (BCC) is the most frequent malignant tumor of the eyelid; it progresses slowly and rarely metastasizes. However, BCC of the eyelid is partially invasive and can extend to the surrounding ocular adnexa even if appropriate treatment is performed. To understand the molecular mechanism underlying its pathogenesis, global gene expression analysis of surgical tissue samples of BCC of the eyelid (n=2) and normal human epidermal keratinocytes was performed using a GeneChip ® system. The histopathological examination of surgically removed eyelid tissues showed the tumor nest composed with small basaloid. In the samples from patients 1 and 2, 687 and 713 genes were identified, respectively, demonstrating ≥5.0-fold higher expression than that noted in normal human epidermal keratinocytes. For the 640 genes with upregulated expression in both patient samples, Ingenuity ® pathway analysis showed that the gene network in BCC of the eyelid included many BCC-associated genes, such as the following: BCL2 apoptosis regulator; Patched-1; and SRY-box 9. In addition, unique gene networks related to cancer cell growth, tumorigenesis, and cell survival were identified. These results of integrating microarray analyses provide further insights into the molecular mechanisms involved in BCC of the eyelid and may provide a therapeutic approach for this disease.

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Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells

Cited by 19 publications

References 57 publications

Rh(III)‐Catalyzed Redox‐Neutral [4+2] Annulation for Direct Assembly of 3‐Acyl Isoquinolin‐1(2H)‐ones as Potent Antitumor Agents

Rh(III)‐Catalyzed Redox‐Neutral [4+2] Annulation for Direct Assembly of 3‐Acyl Isoquinolin‐1(2H)‐ones as Potent Antitumor Agents

Oral toxicity to high level sodium fluoride causes impairment of autophagy

Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling

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