Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway
Abstract
:1. Introduction
2. Results
2.1. In Vitro Radioligand Binding Assays of Sigma-1 Receptor in TNBS-Induced Colitis Rat Colon Tissue
2.2. Effects of Sigma-1 Receptor on the Severity of Inflammation in TNBS Colitis
2.3. Fluvoxamine Increased the Expression of Sigma-1 Receptor in TNBS-Induced Colitis
2.4. Sigma-1 Receptor Agonist Decreased the Activity of the Inflammatory Myeloperoxidase Enzyme
2.5. Sigma-1 Receptor Agonist Fluvoxamine Increased the Expression of UCHL-1 in the Colon
2.6. Sigma-1 Receptor Agonist Attenuated the Levels of IL-6 in the Colon
2.7. Sigma-1 Receptor Agonist Elevated the Activity of the Anti-Inflammatory Heme Oxygenase Enzyme
2.8. Sigma-1 Receptor Agonist Increased the Levels of eNOS and Decreased the Expression of iNOS in the Colon
2.9. Sigma-1 Receptor Agonist Decreased the Expression of NF-κB p65 Subunit
2.10. Sigma-1 Receptor Agonist Decreased the Expression of HMGB1 in the Colon
3. Discussion
4. Materials and Methods
4.1. Drug Preparations
4.2. Radioligand Binding Assays of Sigma-1 Receptor
4.2.1. Preparation of Rat Colon Membrane Homogenates
4.2.2. Radioligand Binding Assays
4.3. Experimental Animals for the Induction of Colitis
4.4. Damage Score and Measurement of the Lesions
4.5. Measurement of the Activity of MPO Proinflammatory Enzyme
4.6. Western Blot Analyses of the Expression of Sigma-1 Receptor, UCHL-1, iNOS, NF-κB p65 and HMGB1
4.7. Determination of IL-6, eNOS Levels in the Colon by ELISA
4.8. Measuring the Activity of HO Anti-Inflammatory Enzyme
4.9. Protein Determination
4.10. Data Representation and Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Treatment | Competition with [3H](+)-Pentazocine | [3H](+)-Pentazocine Saturation Binding | |
---|---|---|---|
Ki ± S.E.M. (nM) | Kd ± S.E.M. (nM) | Bmax ± S.E.M. (fmol/mg) | |
Abs. control | 24 ± 5.1 | 6.4 ± 2.2 | 126 ± 15 |
TNBS | 7.1 ± 1.5 * | 2.4 ± 0.8 | 79 ± 6.5* |
50% EtOH | 5.5 ± 0.9* | 3.5 ± 0.6 | 96 ± 5.2 |
TNBS + FLV | n.d. | 6.7 ± 2.1 | 134 ± 14* |
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Almási, N.; Török, S.; Dvorácskó, S.; Tömböly, C.; Csonka, Á.; Baráth, Z.; Murlasits, Z.; Valkusz, Z.; Pósa, A.; Varga, C.; et al. Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway. Int. J. Mol. Sci. 2020, 21, 4046. https://doi.org/10.3390/ijms21114046
Almási N, Török S, Dvorácskó S, Tömböly C, Csonka Á, Baráth Z, Murlasits Z, Valkusz Z, Pósa A, Varga C, et al. Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway. International Journal of Molecular Sciences. 2020; 21(11):4046. https://doi.org/10.3390/ijms21114046
Chicago/Turabian StyleAlmási, Nikoletta, Szilvia Török, Szabolcs Dvorácskó, Csaba Tömböly, Ákos Csonka, Zoltán Baráth, Zsolt Murlasits, Zsuzsanna Valkusz, Anikó Pósa, Csaba Varga, and et al. 2020. "Lessons on the Sigma-1 Receptor in TNBS-Induced Rat Colitis: Modulation of the UCHL-1, IL-6 Pathway" International Journal of Molecular Sciences 21, no. 11: 4046. https://doi.org/10.3390/ijms21114046