Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus

Abstract Nucleus pulposus (NP) cells reside in a physiologically hyperosmotic environment within the intervertebral disc. TonEBP/NFAT5 is an osmo-sensitive transcription factor that controls expression of genes critical for cell survival under hyperosmotic conditions. A recent report on NP and studi...

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Autores principales:	Chao Liu, Hyowon Choi, Zariel I. Johnson, Jiwei Tian, Irving M. Shapiro, Makarand V. Risbud
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ec6850c9958649eb86cff7b63c20bb32
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spelling	oai:doaj.org-article:ec6850c9958649eb86cff7b63c20bb322021-12-02T12:30:35ZLack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus10.1038/s41598-017-04876-22045-2322https://doaj.org/article/ec6850c9958649eb86cff7b63c20bb322017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04876-2https://doaj.org/toc/2045-2322Abstract Nucleus pulposus (NP) cells reside in a physiologically hyperosmotic environment within the intervertebral disc. TonEBP/NFAT5 is an osmo-sensitive transcription factor that controls expression of genes critical for cell survival under hyperosmotic conditions. A recent report on NP and studies of other cell types have shown that hyperosmolarity triggers autophagy. However, little is known whether such autophagy induction occurs through TonEBP. The goal of this study was to investigate the role of TonEBP in hyperosmolarity-dependent autophagy in NP. Loss-of-function studies showed that autophagy in NP cells was not TonEBP-dependent; hyperosmolarity did not upregulate autophagy as previously reported. NP tissue of haploinsufficient TonEBP mice showed normal pattern of LC3 staining. NP cells did not increase LC3-II or LC3-positive puncta under hyperosmotic conditions. Bafilomycin-A1 treatment and tandem mCherry-EGFP-LC3B reporter transfection demonstrated that the autophagic flux was unaffected by hyperosmolarity. Even under serum-free conditions, NP cells did not induce autophagy with increasing osmolarity. Hyperosmolarity did not change the phosphorylation of ULK1 by mTOR and AMPK. An ex vivo disc organ culture study supported that extracellular hyperosmolarity plays no role in promoting autophagy in the NP. We conclude that hyperosmolarity does not play a role in autophagy induction in NP cells.Chao LiuHyowon ChoiZariel I. JohnsonJiwei TianIrving M. ShapiroMakarand V. RisbudNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chao Liu Hyowon Choi Zariel I. Johnson Jiwei Tian Irving M. Shapiro Makarand V. Risbud Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
description	Abstract Nucleus pulposus (NP) cells reside in a physiologically hyperosmotic environment within the intervertebral disc. TonEBP/NFAT5 is an osmo-sensitive transcription factor that controls expression of genes critical for cell survival under hyperosmotic conditions. A recent report on NP and studies of other cell types have shown that hyperosmolarity triggers autophagy. However, little is known whether such autophagy induction occurs through TonEBP. The goal of this study was to investigate the role of TonEBP in hyperosmolarity-dependent autophagy in NP. Loss-of-function studies showed that autophagy in NP cells was not TonEBP-dependent; hyperosmolarity did not upregulate autophagy as previously reported. NP tissue of haploinsufficient TonEBP mice showed normal pattern of LC3 staining. NP cells did not increase LC3-II or LC3-positive puncta under hyperosmotic conditions. Bafilomycin-A1 treatment and tandem mCherry-EGFP-LC3B reporter transfection demonstrated that the autophagic flux was unaffected by hyperosmolarity. Even under serum-free conditions, NP cells did not induce autophagy with increasing osmolarity. Hyperosmolarity did not change the phosphorylation of ULK1 by mTOR and AMPK. An ex vivo disc organ culture study supported that extracellular hyperosmolarity plays no role in promoting autophagy in the NP. We conclude that hyperosmolarity does not play a role in autophagy induction in NP cells.
format	article
author	Chao Liu Hyowon Choi Zariel I. Johnson Jiwei Tian Irving M. Shapiro Makarand V. Risbud
author_facet	Chao Liu Hyowon Choi Zariel I. Johnson Jiwei Tian Irving M. Shapiro Makarand V. Risbud
author_sort	Chao Liu
title	Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
title_short	Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
title_full	Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
title_fullStr	Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
title_full_unstemmed	Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
title_sort	lack of evidence for involvement of tonebp and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ec6850c9958649eb86cff7b63c20bb32
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Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus

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