Low-Dose Dioxin Reduced Glucose Uptake in C2C12 Myocytes: The Role of Mitochondrial Oxidative Stress and Insulin-Dependent Calcium Mobilization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and Treatment
2.2. Plasmids and Transfection
2.3. Enzymatic Assay for 2-Deoxyglucose Uptake
2.4. Assays for GLUT4 Translocation
2.5. Western Blot
2.6. Real-Time Quantitative RT-PCR
2.7. Assays for Mitochondrial Activity
2.8. Measurement of Oxygen Consumption Rate
2.9. OXPHOS Complex I Activity
2.10. Calcium Monitoring
2.11. Measurement of Glucose Uptake in Mouse Muscles
2.12. Statistical Analysis
3. Results
3.1. Inhibition of Insulin-Triggered Glucose Uptake by TCDD
3.2. Low-Dose TCDD Reduced IRβ and IRS-1 Protein Expression without Affecting Akt Phosphorylation
3.3. TCDD Impaired Mitochondrial Activity
3.4. TCDD Increased OXPHOS Complex I Activity and Mitochondrial ROS
3.5. TCDD Disturbed the Insulin-Triggered Calcium Release into Cytosol
3.6. AhR-Independent Effects of TCDD in Skeletal Muscle
3.7. Calcium Dysregulation Resulted from Mitochondrial ROS
3.8. MitoTEMPO Protected from TCDD-Induced Insulin Resistance in the Absence of AhR
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Genes | Accession Number | Forward Sequence (5′→3′) | Reverse Sequence (5′→3′) |
---|---|---|---|
AHR | NM_013464 | GTGTGCAGTTGGACTTCCCT | TGGCTGGCACTGATACATGG |
CYP1A1 | NM_009992 | TCCGGCATTCATCCTTCGTC | ACAGTTCCCGGTCATGGTTA |
MCU | NM_001033259 | TGATGACGTGACGGTGGTTT | CGAACGCCATCTGGTGAGTA |
PKM2 | NM_011099 | AGCACCTGATTGCCCGAGAG | GTGAGCACGATAATGGCCCC |
LDHA | NM_010699 | AATGAAGGACTTGGCGGATG | ATGACCAGCTTGGAGTTCGC |
LDHB | NM_008492 | TGGTGGACAGTGCCTATGAAG | CATTGAGGATGCACGGGAGA |
NRF2 | NM_010902 | 5′-TTCTCCGCTGCTCGGACTA | ATGTCTTGCCTCCAAAGGATGT |
NQO1 | NM_008706 | TAGCCTGTAGCCAGCCCTAA | GCCTCCTTCATGGCGTAGTT |
18S rRNA | NR_003278 | GAGCGAAAGCATTTGCCAAG | GGCATCGTTTATGGTCGGAA |
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Im, S.; Kang, S.; Kim, J.H.; Oh, S.J.; Pak, Y.K. Low-Dose Dioxin Reduced Glucose Uptake in C2C12 Myocytes: The Role of Mitochondrial Oxidative Stress and Insulin-Dependent Calcium Mobilization. Antioxidants 2022, 11, 2109. https://doi.org/10.3390/antiox11112109
Im S, Kang S, Kim JH, Oh SJ, Pak YK. Low-Dose Dioxin Reduced Glucose Uptake in C2C12 Myocytes: The Role of Mitochondrial Oxidative Stress and Insulin-Dependent Calcium Mobilization. Antioxidants. 2022; 11(11):2109. https://doi.org/10.3390/antiox11112109
Chicago/Turabian StyleIm, Suyeol, Sora Kang, Ji Hwan Kim, Seung Jun Oh, and Youngmi Kim Pak. 2022. "Low-Dose Dioxin Reduced Glucose Uptake in C2C12 Myocytes: The Role of Mitochondrial Oxidative Stress and Insulin-Dependent Calcium Mobilization" Antioxidants 11, no. 11: 2109. https://doi.org/10.3390/antiox11112109