Torrealba, Natalia;
Navarro-Marquez, Mario;
Garrido, Valeria;
Pedrozo, Zully;
Romero, Diego;
Eura, Yuka;
Villalobos, Elisa;
... Lavandero, Sergio; + view all
(2017)
Herpud1 negatively regulates pathological cardiac hypertrophy by inducing IP3 receptor degradation.
Scientific Reports
, 7
, Article 13402. 10.1038/s41598-017-13797-z.
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Abstract
Cardiac hypertrophy is an adaptive response triggered by pathological stimuli. Regulation of the synthesis and the degradation of the Ca2+ channel inositol 1,4,5-trisphosphate receptor (IP3R) affects progression to cardiac hypertrophy. Herpud1, a component of the endoplasmic reticulum-associated degradation (ERAD) complex, participates in IP3R1 degradation and Ca2+ signaling, but the cardiac function of Herpud1 remains unknown. We hypothesize that Herpud1 acts as a negative regulator of cardiac hypertrophy by regulating IP3R protein levels. Our results show that Herpud1-knockout mice exhibit cardiac hypertrophy and dysfunction and that decreased Herpud1 protein levels lead to elevated levels of hypertrophic markers in cultured rat cardiomyocytes. In addition, IP3R levels were elevated both in Herpud1-knockout mice and Herpud1 siRNA-treated rat cardiomyocytes. The latter treatment also led to elevated cytosolic and nuclear Ca2+ levels. In summary, the absence of Herpud1 generates a pathological hypertrophic phenotype by regulating IP3R protein levels. Herpud1 is a novel negative regulator of pathological cardiac hypertrophy.
| Type: | Article |
|---|---|
| Title: | Herpud1 negatively regulates pathological cardiac hypertrophy by inducing IP3 receptor degradation |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-13797-z |
| Publisher version: | https://doi.org/10.1038/s41598-017-13797-z |
| Language: | English |
| Additional information: | © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Cardiac hypertrophy, Cell signalling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10213202 |
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