Cathepsin K knockout protects against cardiac dysfunction in diabetic mice

Abstract Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated card...

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Autores principales:	Rui Guo, Yinan Hua, Olivia Rogers, Travis E. Brown, Jun Ren, Sreejayan Nair
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b8fb529c4fd4d61ad3057b47f7187a9
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spelling	oai:doaj.org-article:2b8fb529c4fd4d61ad3057b47f7187a92021-12-02T16:06:51ZCathepsin K knockout protects against cardiac dysfunction in diabetic mice10.1038/s41598-017-09037-z2045-2322https://doaj.org/article/2b8fb529c4fd4d61ad3057b47f7187a92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09037-zhttps://doaj.org/toc/2045-2322Abstract Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections. Body weight, organ mass, fasting blood glucose, energy expenditure, cardiac geometry and function, cardiac histomorphology, glutathione levels and protein levels of cathepsin K and those associated with Ca2+ handling, calcineurin/NFAT signaling, insulin signaling, cardiac apoptosis and fibrosis were determined. STZ-induced diabetic mice exhibited distinct cardiac dysfunction, dampened intracellular calcium handling, alterations in cardiac morphology, and elevated cardiomyocyte apoptosis, which were mitigated in the cathepsin K knockout mice. Additionally, cathepsin K knockout mice attenuated cardiac oxidative stress and calcineurin/NFAT signaling in diabetic mice. In cultured H9c2 myoblasts, pharmacological inhibition of cathepsin K, or treatment with calcineurin inhibitor rescued cells from high-glucose triggered oxidative stress and apoptosis. Therefore, cathepsin K may represent a potential target in treating diabetes-associated cardiac dysfunction.Rui GuoYinan HuaOlivia RogersTravis E. BrownJun RenSreejayan NairNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rui Guo Yinan Hua Olivia Rogers Travis E. Brown Jun Ren Sreejayan Nair Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
description	Abstract Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections. Body weight, organ mass, fasting blood glucose, energy expenditure, cardiac geometry and function, cardiac histomorphology, glutathione levels and protein levels of cathepsin K and those associated with Ca2+ handling, calcineurin/NFAT signaling, insulin signaling, cardiac apoptosis and fibrosis were determined. STZ-induced diabetic mice exhibited distinct cardiac dysfunction, dampened intracellular calcium handling, alterations in cardiac morphology, and elevated cardiomyocyte apoptosis, which were mitigated in the cathepsin K knockout mice. Additionally, cathepsin K knockout mice attenuated cardiac oxidative stress and calcineurin/NFAT signaling in diabetic mice. In cultured H9c2 myoblasts, pharmacological inhibition of cathepsin K, or treatment with calcineurin inhibitor rescued cells from high-glucose triggered oxidative stress and apoptosis. Therefore, cathepsin K may represent a potential target in treating diabetes-associated cardiac dysfunction.
format	article
author	Rui Guo Yinan Hua Olivia Rogers Travis E. Brown Jun Ren Sreejayan Nair
author_facet	Rui Guo Yinan Hua Olivia Rogers Travis E. Brown Jun Ren Sreejayan Nair
author_sort	Rui Guo
title	Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
title_short	Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
title_full	Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
title_fullStr	Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
title_full_unstemmed	Cathepsin K knockout protects against cardiac dysfunction in diabetic mice
title_sort	cathepsin k knockout protects against cardiac dysfunction in diabetic mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2b8fb529c4fd4d61ad3057b47f7187a9
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_version_	1718384832081297408

Cathepsin K knockout protects against cardiac dysfunction in diabetic mice

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