Regulation of PUMA induced by mechanical stress in rat cardiomyocytes

Wen Pin Cheng, Gong-Jhe Wu, Bao Wei Wang, Kou-Gi Shyu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: PUMA (p53-up-regulated modulator of apoptosis), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of PUMA in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes. Methods: Aorta-caval (AV) shunt was performed in adult Wistar rats to induce volume overload. Rat neonatal cardiomyocytes were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. Results: PUMA protein and mRNA were up-regulated in the shunt group as compared with sham group. The increased PUMA protein expression and apoptosis induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited the apoptosis induced by volume overload. Cyclic stretch significantly enhanced PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-gamaa (INF-gamma) antibody 30 min before stretch reduced the induction of PUMA protein. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid, SP600125 and INF-gamaa antibody abolished the PUMA promoter activity induced by stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA and atorvastatin. Conclusions: Mechanical stress enhanced apoptosis and PUMA expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.

Original languageEnglish
Article number72
JournalJournal of Biomedical Science
Volume19
Issue number1
DOIs
Publication statusPublished - 2012

Fingerprint

Mechanical Stress
Cardiac Myocytes
Modulators
Rats
Apoptosis
JNK Mitogen-Activated Protein Kinases
Small Interfering RNA
Assays
Proteins
Interferon Regulatory Factor-1
Venae Cavae

Keywords

  • Atorvastatin
  • Cardiomyocytes
  • Cyclic stretch
  • PUMA
  • Volume overload

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

Cite this

Regulation of PUMA induced by mechanical stress in rat cardiomyocytes. / Cheng, Wen Pin; Wu, Gong-Jhe; Wang, Bao Wei; Shyu, Kou-Gi.

In: Journal of Biomedical Science, Vol. 19, No. 1, 72, 2012.

Research output: Contribution to journalArticle

Cheng, Wen Pin ; Wu, Gong-Jhe ; Wang, Bao Wei ; Shyu, Kou-Gi. / Regulation of PUMA induced by mechanical stress in rat cardiomyocytes. In: Journal of Biomedical Science. 2012 ; Vol. 19, No. 1.
@article{91582287e9ad4ef3b8438f61075d0030,
title = "Regulation of PUMA induced by mechanical stress in rat cardiomyocytes",
abstract = "Background: PUMA (p53-up-regulated modulator of apoptosis), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of PUMA in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes. Methods: Aorta-caval (AV) shunt was performed in adult Wistar rats to induce volume overload. Rat neonatal cardiomyocytes were stretched by vacuum to 20{\%} of maximum elongation at 60 cycles/min. Results: PUMA protein and mRNA were up-regulated in the shunt group as compared with sham group. The increased PUMA protein expression and apoptosis induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited the apoptosis induced by volume overload. Cyclic stretch significantly enhanced PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-gamaa (INF-gamma) antibody 30 min before stretch reduced the induction of PUMA protein. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid, SP600125 and INF-gamaa antibody abolished the PUMA promoter activity induced by stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA and atorvastatin. Conclusions: Mechanical stress enhanced apoptosis and PUMA expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.",
keywords = "Atorvastatin, Cardiomyocytes, Cyclic stretch, PUMA, Volume overload",
author = "Cheng, {Wen Pin} and Gong-Jhe Wu and Wang, {Bao Wei} and Kou-Gi Shyu",
year = "2012",
doi = "10.1186/1423-0127-19-72",
language = "English",
volume = "19",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Regulation of PUMA induced by mechanical stress in rat cardiomyocytes

AU - Cheng, Wen Pin

AU - Wu, Gong-Jhe

AU - Wang, Bao Wei

AU - Shyu, Kou-Gi

PY - 2012

Y1 - 2012

N2 - Background: PUMA (p53-up-regulated modulator of apoptosis), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of PUMA in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes. Methods: Aorta-caval (AV) shunt was performed in adult Wistar rats to induce volume overload. Rat neonatal cardiomyocytes were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. Results: PUMA protein and mRNA were up-regulated in the shunt group as compared with sham group. The increased PUMA protein expression and apoptosis induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited the apoptosis induced by volume overload. Cyclic stretch significantly enhanced PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-gamaa (INF-gamma) antibody 30 min before stretch reduced the induction of PUMA protein. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid, SP600125 and INF-gamaa antibody abolished the PUMA promoter activity induced by stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA and atorvastatin. Conclusions: Mechanical stress enhanced apoptosis and PUMA expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.

AB - Background: PUMA (p53-up-regulated modulator of apoptosis), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of PUMA in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes. Methods: Aorta-caval (AV) shunt was performed in adult Wistar rats to induce volume overload. Rat neonatal cardiomyocytes were stretched by vacuum to 20% of maximum elongation at 60 cycles/min. Results: PUMA protein and mRNA were up-regulated in the shunt group as compared with sham group. The increased PUMA protein expression and apoptosis induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited the apoptosis induced by volume overload. Cyclic stretch significantly enhanced PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-gamaa (INF-gamma) antibody 30 min before stretch reduced the induction of PUMA protein. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid, SP600125 and INF-gamaa antibody abolished the PUMA promoter activity induced by stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA and atorvastatin. Conclusions: Mechanical stress enhanced apoptosis and PUMA expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.

KW - Atorvastatin

KW - Cardiomyocytes

KW - Cyclic stretch

KW - PUMA

KW - Volume overload

UR - http://www.scopus.com/inward/record.url?scp=84864499710&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864499710&partnerID=8YFLogxK

U2 - 10.1186/1423-0127-19-72

DO - 10.1186/1423-0127-19-72

M3 - Article

VL - 19

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 1

M1 - 72

ER -