Overexpression of protein phosphatase 5 in the mouse heart: Reduced contractility but increased stress tolerance - Two sides of the same coin?

Ulrich Gergs; Tina Jahn; Franziska Werner; Carolin Köhler; Friedrich Köpp; Claudia Großmann; Joachim Neumann

doi:10.1371/journal.pone.0221289

Overexpression of protein phosphatase 5 in the mouse heart: Reduced contractility but increased stress tolerance - Two sides of the same coin?

PLoS One. 2019 Aug 19;14(8):e0221289. doi: 10.1371/journal.pone.0221289. eCollection 2019.

Authors

Ulrich Gergs¹, Tina Jahn¹, Franziska Werner¹, Carolin Köhler¹, Friedrich Köpp¹, Claudia Großmann², Joachim Neumann¹

Affiliations

¹ Institut für Pharmakologie und Toxikologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
² Julius-Bernstein-Institut für Physiologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.

Abstract

The pathophysiological mechanisms of sepsis-induced cardiac dysfunction are largely unknown. The Toll-like receptor 4 (TLR4) is expressed in cardiac myocytes and is involved in bacterial endotoxin-mediated inflammatory disorders. TLR4 signaling leads to activation of the nuclear factor kappa B followed by increased expression of cytokines. Several protein phosphatases including PP2Cβ, PP2A or PP1 are known to act as regulators of this signaling pathway. Here, we examined the role of PP5 for the inflammatory response to the bacterial endotoxin lipopolysaccharide in the heart using a transgenic mouse model with cardiac myocyte directed overexpression of PP5. In these transgenic mice, basal cardiac contractility was reduced, in vivo as well as in vitro, but LPS-induced cardiac dysfunction was less pronounced compared to wild type mice. Quantitative RT-PCR suggested an attenuated NF-κB signaling in the heart and cardiac expression of heat shock protein 25 (HSP25) was increased in PP5 transgenic mice. From our data we assume that PP5 increases stress tolerance of cardiac myocytes by downregulation of NF-κB signaling and upregulation of HSP25 expression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Disease Models, Animal
Down-Regulation
Echocardiography
Female
Heart Failure / diagnosis
Heart Failure / immunology*
Heat-Shock Proteins / metabolism
Humans
Isolated Heart Preparation
Lipopolysaccharides / toxicity
Male
Mice
Mice, Transgenic
Molecular Chaperones / metabolism
Myocardial Contraction / immunology
Myocytes, Cardiac / immunology*
Myocytes, Cardiac / metabolism
NF-kappa B / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / immunology*
Nuclear Proteins / metabolism
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / immunology*
Phosphoprotein Phosphatases / metabolism
Sepsis / complications*
Sepsis / immunology
Sepsis / microbiology
Signal Transduction / immunology
Toll-Like Receptor 4 / metabolism*
Up-Regulation

Substances

Heat-Shock Proteins
Hsbp1 protein, mouse
Lipopolysaccharides
Molecular Chaperones
NF-kappa B
Nuclear Proteins
Tlr4 protein, mouse
Toll-Like Receptor 4
Phosphoprotein Phosphatases
protein phosphatase 5

Grants and funding

The authors received financial support within the funding program Open Access Publishing by the German Research Foundation (DFG) for the article processing charge of this manuscript.