Parathyroid hormone-related peptide protects cardiomyocytes from oxidative stress-induced cell death: First evidence of a novel endocrine–cardiovascular interaction

Although there is a growing interest in the molecular cross-talk between the endocrine and cardiovascular systems, the cardiac effects of calcium-regulating hormones (i.e., parathyroid hormone-related peptide (PTHrP)) have not been explored. In this study, we examined the effect of PTHrP on the viab...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2015-12, Vol.468 (1-2), p.202-207
Main Authors: Datta, Nabanita S., Chukkapalli, Sahiti, Vengalil, Nathan, Zhan, Enbo, Przyklenk, Karin, Lasley, Robert
Format: Article
Language:English
Subjects:
Animals
Cardioprotection
Cell Death
Cells, Cultured
Dual Specificity Phosphatase 1 - genetics
Dual Specificity Phosphatase 1 - metabolism
Male
MAPK phosphatase-1
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocytes, Cardiac - cytology
Myocytes, Cardiac - metabolism
Oxidative Stress
Parathyroid Hormone-Related Protein - metabolism
Phosphatidylinositol 3-Kinases - metabolism
PI3K/AKT
Proto-Oncogene Proteins c-akt - metabolism
PTHrP
Signal Transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Although there is a growing interest in the molecular cross-talk between the endocrine and cardiovascular systems, the cardiac effects of calcium-regulating hormones (i.e., parathyroid hormone-related peptide (PTHrP)) have not been explored. In this study, we examined the effect of PTHrP on the viability of isolated adult mouse cardiomyocytes subjected to oxidative stress. Myocytes from 19 to 22 week old male 129J/C57BL6 mice were exposed to oxidative insult in the form of H2O2 which led to more than 70% loss of cell viability. Herein we demonstrate, for the first time, that pretreatment with 100 nM PTHrP prior to 100 μM H2O2 incubation prevents H2O2 -induced cell death by more than 50%. Immunoblot analysis revealed H2O2 induction of MKP-1 protein expression while PTHrP decreased MKP-1 expression. Moreover, myocytes derived from MKP1 KO mice were resistant to oxidative injury. No added benefit of PTHrP treatment was noted in MKP-1 null cardiomyocytes. Using specific pharmacological inhibitors we demonstrated that P-p38, P-ERK and P-AKT mediated PTHrP's cardioprotective action. These data provide novel evidence that: i) down-regulation of MKP1 affords profound protection against oxidative stress; and ii) PTHrP is cardioprotective, possibly via down-regulation of MKP-1 and activation of MAPK and PI3K/AKT signaling. •PTHrP protects isolated cardiomyocytes from oxidative stress-induced cell death.•Down-regulation of MKP-1 affords profound protection against oxidative stress.•PTHrP regulation of cardioprotection involves MKP-1, MAPKs and AKT.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2015.10.130