Overexpression of protein phosphatase 5 in the mouse heart: Reduced contractility but increased stress tolerance - Two sides of the same coin?
Ulrich GergsTina JahnFranziska WernerCarolin KöhlerFriedrich KöppClaudia GroßmannJoachim NeumannPublished in: PloS one (2019)
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.
Keyphrases
- nuclear factor
- toll like receptor
- lps induced
- inflammatory response
- signaling pathway
- heat shock protein
- left ventricular
- poor prognosis
- oxidative stress
- heart failure
- mouse model
- cell proliferation
- immune response
- transcription factor
- pi k akt
- intensive care unit
- atrial fibrillation
- wild type
- epithelial mesenchymal transition
- type diabetes
- heat shock
- metabolic syndrome
- small molecule
- insulin resistance
- diabetic rats
- high glucose
- drug induced
- protein kinase