Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes

Abstract Glucocorticoids (GCs) are rapidly released in response to stress and play an important role in the physiological adjustments to re-establish homeostasis. The mode of action of GCs for stress coping is mediated largely by the steroid binding to the glucocorticoid receptor (GR), a ligand-boun...

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Autores principales:	Chinmayee Das, Manoj K. Rout, Willem C. Wildering, Mathilakath M. Vijayan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bef03e3bc2e14600a0ebef210ecd67c3
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spelling	oai:doaj.org-article:bef03e3bc2e14600a0ebef210ecd67c32021-12-02T14:49:33ZCortisol modulates calcium release-activated calcium channel gating in fish hepatocytes10.1038/s41598-021-88957-32045-2322https://doaj.org/article/bef03e3bc2e14600a0ebef210ecd67c32021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88957-3https://doaj.org/toc/2045-2322Abstract Glucocorticoids (GCs) are rapidly released in response to stress and play an important role in the physiological adjustments to re-establish homeostasis. The mode of action of GCs for stress coping is mediated largely by the steroid binding to the glucocorticoid receptor (GR), a ligand-bound transcription factor, and modulating the expression of target genes. However, GCs also exert rapid actions that are independent of transcriptional regulation by modulating second messenger signaling. However, a membrane-specific protein that transduces rapid GCs signal is yet to be characterized. Here, using freshly isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) and fura2 fluorescence microscopy, we report that stressed levels of cortisol rapidly stimulate the rise in cytosolic free calcium ([Ca2+]i). Pharmacological manipulations using specific extra- and intra-cellular calcium chelators, plasma membrane and endoplasmic reticulum channel blockers and receptors, indicated extracellular Ca2+ entry is required for the cortisol-mediated rise in ([Ca2+]i). Particularly, the calcium release-activated calcium (CRAC) channel gating appears to be a key target for the rapid action of cortisol in the ([Ca2+]i) rise in trout hepatocytes. To test this further, we carried out in silico molecular docking studies using the Drosophila CRAC channel modulator 1 (ORAI1) protein, the pore forming subunit of CRAC channel that is highly conserved. The result predicts a putative binding site on CRAC for cortisol to modulate channel gating, suggesting a direct, as well as an indirect regulation (by other membrane receptors) of CRAC channel gating by cortisol. Altogether, CRAC channel may be a novel cortisol-gated Ca2+ channel transducing rapid nongenomic signalling in hepatocytes during acute stress.Chinmayee DasManoj K. RoutWillem C. WilderingMathilakath M. VijayanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chinmayee Das Manoj K. Rout Willem C. Wildering Mathilakath M. Vijayan Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
description	Abstract Glucocorticoids (GCs) are rapidly released in response to stress and play an important role in the physiological adjustments to re-establish homeostasis. The mode of action of GCs for stress coping is mediated largely by the steroid binding to the glucocorticoid receptor (GR), a ligand-bound transcription factor, and modulating the expression of target genes. However, GCs also exert rapid actions that are independent of transcriptional regulation by modulating second messenger signaling. However, a membrane-specific protein that transduces rapid GCs signal is yet to be characterized. Here, using freshly isolated hepatocytes from rainbow trout (Oncorhynchus mykiss) and fura2 fluorescence microscopy, we report that stressed levels of cortisol rapidly stimulate the rise in cytosolic free calcium ([Ca2+]i). Pharmacological manipulations using specific extra- and intra-cellular calcium chelators, plasma membrane and endoplasmic reticulum channel blockers and receptors, indicated extracellular Ca2+ entry is required for the cortisol-mediated rise in ([Ca2+]i). Particularly, the calcium release-activated calcium (CRAC) channel gating appears to be a key target for the rapid action of cortisol in the ([Ca2+]i) rise in trout hepatocytes. To test this further, we carried out in silico molecular docking studies using the Drosophila CRAC channel modulator 1 (ORAI1) protein, the pore forming subunit of CRAC channel that is highly conserved. The result predicts a putative binding site on CRAC for cortisol to modulate channel gating, suggesting a direct, as well as an indirect regulation (by other membrane receptors) of CRAC channel gating by cortisol. Altogether, CRAC channel may be a novel cortisol-gated Ca2+ channel transducing rapid nongenomic signalling in hepatocytes during acute stress.
format	article
author	Chinmayee Das Manoj K. Rout Willem C. Wildering Mathilakath M. Vijayan
author_facet	Chinmayee Das Manoj K. Rout Willem C. Wildering Mathilakath M. Vijayan
author_sort	Chinmayee Das
title	Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
title_short	Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
title_full	Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
title_fullStr	Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
title_full_unstemmed	Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
title_sort	cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bef03e3bc2e14600a0ebef210ecd67c3
work_keys_str_mv	AT chinmayeedas cortisolmodulatescalciumreleaseactivatedcalciumchannelgatinginfishhepatocytes AT manojkrout cortisolmodulatescalciumreleaseactivatedcalciumchannelgatinginfishhepatocytes AT willemcwildering cortisolmodulatescalciumreleaseactivatedcalciumchannelgatinginfishhepatocytes AT mathilakathmvijayan cortisolmodulatescalciumreleaseactivatedcalciumchannelgatinginfishhepatocytes
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Cortisol modulates calcium release-activated calcium channel gating in fish hepatocytes

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