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Activation of Cx43 Hemichannels Induces the Generation of Ca 2+ Oscillations in White Adipocytes and Stimulates Lipolysis.
- Source :
- International Journal of Molecular Sciences; Aug2021, Vol. 22 Issue 15, p8095-8095, 1p
- Publication Year :
- 2021
-
Abstract
- The aim of the study was to investigate the mechanisms of Ca<superscript>2+</superscript> oscillation generation upon activation of connexin-43 and regulation of the lipolysis/lipogenesis balance in white adipocytes through vesicular ATP release. With fluorescence microscopy it was revealed that a decrease in the concentration of extracellular calcium ([Ca<superscript>2+</superscript>]<subscript>ex</subscript>) results in two types of Ca<superscript>2+</superscript> responses in white adipocytes: Ca<superscript>2+</superscript> oscillations and transient Ca<superscript>2+</superscript> signals. It was found that activation of the connexin half-channels is involved in the generation of Ca<superscript>2+</superscript> oscillations, since the blockers of the connexin hemichannels—carbenoxolone, octanol, proadifen and Gap26—as well as Cx43 gene knockdown led to complete suppression of these signals. The activation of Cx43 in response to the reduction of [Ca<superscript>2+</superscript>]<subscript>ex</subscript> was confirmed by TIRF microscopy. It was shown that in response to the activation of Cx43, ATP-containing vesicles were released from the adipocytes. This process was suppressed by knockdown of the Cx43 gene and by bafilomycin A1, an inhibitor of vacuolar ATPase. At the level of intracellular signaling, the generation of Ca<superscript>2+</superscript> oscillations in white adipocytes in response to a decrease in [Ca<superscript>2+</superscript>]<subscript>ex</subscript> occurred due to the mobilization of the Ca<superscript>2+</superscript> ions from the thapsigargin-sensitive Ca<superscript>2+</superscript> pool of IP<subscript>3</subscript>R as a result of activation of the purinergic P2Y1 receptors and phosphoinositide signaling pathway. After activation of Cx43 and generation of the Ca<superscript>2+</superscript> oscillations, changes in the expression levels of key genes and their encoding proteins involved in the regulation of lipolysis were observed in white adipocytes. This effect was accompanied by a decrease in the number of adipocytes containing lipid droplets, while inhibition or knockdown of Cx43 led to inhibition of lipolysis and accumulation of lipid droplets. In this study, we investigated the mechanism of Ca<superscript>2+</superscript> oscillation generation in white adipocytes in response to a decrease in the concentration of Ca<superscript>2+</superscript> ions in the external environment and established an interplay between periodic Ca<superscript>2+</superscript> modes and the regulation of the lipolysis/lipogenesis balance. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 22
- Issue :
- 15
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 151783736
- Full Text :
- https://doi.org/10.3390/ijms22158095