Glibenclamide Prevents Inflammation by Targeting NLRP3 Inflammasome Activation In Vitro

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Аннотация

The NLRP3 inflammasome is known to play a significant role in the development of neurodegeneration and physiological aging, as well as the development of metabolic inflammation, which has generated significant interest in the scientific community in finding effective inhibitors of the NLRP3 inflammasome and assessing their effects. The purpose of this study was to evaluate the effect of pharmacological modulation of NLRP3 activity using an indirect NLRP3 inflammasome inhibitor, glibenclamide, on the expression of metaflammasome components in in vitro brain cells obtained from middle-aged mice. The study revealed that glibenclamide reduces the expression of pro-inflammatory markers NLRP3 and IL18 in cell culture, which in turn leads to the prevention of phosphorylation of protein kinases of the metaflammasome complex – PKR and IKKβ. However, we did not observe changes in the expression of pathologically phosphorylated IRS, as well as in the number of senescent cells in cultures after the exposure to glibenclamide.

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Авторлар туралы

E. Khilazheva

Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Ministry of Healthcare of the Russian Federation; Research Institute of Molecular Medicine and Pathobiochemistry, Educational Institution of Higher Education «Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University» of the Ministry of Healthcare of the Russian Federation

Email: yuliakomleva@mail.ru
Ресей, Krasnoyarsk; Krasnoyarsk

Yu. Panina

Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Ministry of Healthcare of the Russian Federation; Research Institute of Molecular Medicine and Pathobiochemistry, Educational Institution of Higher Education «Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University» of the Ministry of Healthcare of the Russian Federation

Email: yuliakomleva@mail.ru
Ресей, Krasnoyarsk; Krasnoyarsk

A. Mosiagina

Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Ministry of Healthcare of the Russian Federation; Research Institute of Molecular Medicine and Pathobiochemistry, Educational Institution of Higher Education «Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University» of the Ministry of Healthcare of the Russian Federation

Email: yuliakomleva@mail.ru
Ресей, Krasnoyarsk; Krasnoyarsk

O. Belozor

Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University of the Ministry of Healthcare of the Russian Federation; Research Institute of Molecular Medicine and Pathobiochemistry, Educational Institution of Higher Education «Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University» of the Ministry of Healthcare of the Russian Federation

Email: yuliakomleva@mail.ru
Ресей, Krasnoyarsk; Krasnoyarsk

Yu. Komleva

Brain Institute, Scientific Center of Neurology

Хат алмасуға жауапты Автор.
Email: yuliakomleva@mail.ru
Ресей, Moscow

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2. Fig. 1. Co-culture of astrocytes and neurons obtained from mice at the age of 14 months: cell nuclei are stained with DAPI (blue), expression of astrocyte marker GFAP (green) and neuron marker NeuN (red) is shown. The scale is 50 microns.

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3. Fig. 2. (a) – quantitative analysis of NLRP3 expression in cell culture in experimental groups. (b) – representative images of NLRP3 expression (green) by cells. The cell nuclei are stained with DAPI (blue). The scale is 50 – microns. ** – the level of statistical significance, p < 0.01.

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4. Fig. 3. (a) – quantitative analysis of IL18 expression in cell culture in experimental groups. (b) – representative images of IL18 expression (green) by cells. The cell nuclei are stained with DAPI (blue). The scale is 30 microns. ** – the level of statistical significance, p < 0.01.

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5. Fig. 4. (a) – quantitative analysis of SA-β-gal+ cells, presented in the form of optical density in CU in cell culture. (b) – representative images of SA-β-gal staining in vitro. The scale is 100 microns.

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6. Figure 5. (a) – quantitative analysis of HMGB1 expression in cell culture in experimental groups. (b) – representative images of HMGB1 expression (red) by cells. The cell nuclei are stained with DAPI (blue). The scale is 50 microns.

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7. Figure 6. (a) – quantitative analysis of PKR expression in cell culture in experimental groups. (b) – representative images of PKR expression (red) by cells. The cell nuclei are stained with DAPI (blue). The scale is 30 microns. * – the level of statistical significance, p < 0.05.

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8. Fig. 7. (a) – quantitative analysis of p-IKKbeta expression in cell culture in experimental groups. (b) – representative images of p-IKKbeta expression (red) by cells. The cell nuclei are stained with DAPI (blue). The scale is 50 microns. ** – the level of statistical significance, p < 0.01.

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9. Figure 8. (a) – quantitative analysis of pIRS-Ser expression in cell culture in experimental groups. (b) – representative images of the expression of pIRS-Ser (red) by cells. The cell nuclei are stained with DAPI (blue). The scale is 50 microns.

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10. Fig. 9. (a) – a summary diagram of amplitudes; (b) – a summary diagram of the values of the rise time; (c) – a summary diagram of the values of the slope of the CPT of the hippocampal CA1 zone; (d) – a summary diagram of the changes in the slope of the CPT after tetanus stimulation of the hippocampal CA1 zone. * – the level of statistical significance, p < 0.05.

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