Key result
Inhibition of PARP-1 enhanced DNA binding and transactivation of PPAR gamma, increasing the transcription of adiponectin and AdipoR1 in cultured rat cardiac fibroblasts.
Why the study?
Does PARP-1 inhibition increase adiponectin and AdipoR1 expression in cultured rat cardiac fibroblasts?
Does PARP-1 inhibition increase adiponectin and AdipoR1 expression in cultured rat cardiac fibroblasts?
PARP-1 inhibits adiponectin and AdipoR1 expression through poly(ADP-ribosyl)ation of PPAR gamma in cardiac fibroblasts, suggesting PARP-1 inhibition as a potential mechanism to upregulate cardioprotective adiponectin.
Hypothesis-generating for PARP-1 inhibition in cardiac fibroblasts; leaves open translation to in vivo or human disease.
AIMS: Our aim was to explore the mechanism underlying the transcriptional regulation of adiponectin and its receptors (AdipoR) in cultured rat cardiac fibroblasts. METHODS AND RESULTS: Using western blot and real-time RT-PCR assays, the expression of adiponectin and its receptors was determined. Using Southwestern blot and electrophoretic mobility shift assays, the DNA binding activity of peroxisome proliferator activated receptor gamma (PPAR gamma) was determined. The results showed that adiponectin and AdipoR1 were highly expressed in cultured rat cardiac fibroblasts. Inhibition of poly(ADP-ribose) polymerase 1 (PARP-1) by 3-aminobenzamide, PJ34, or PARP-1 siRNA markedly increased the transcription of adiponectin and AdipoR1 in cultured fibroblasts, mature 3T3 L1 adipocytes, rat myocardium, and white adipose tissue. PPAR gamma was poly(ADP-ribosyl)ated by PARP-1 in cardiac fibroblasts under basal conditions. Poly(ADP-ribosyl)ation of PPAR gamma prevented its binding to DNA. Inhibition of PARP-1 enhanced the DNA binding and transactivation of PPAR gamma and increased the transcription of PPAR gamma-target genes including CD36, lipoprotein lipase, and leptin in cultured fibroblasts. CONCLUSION: PARP-1 inhibits adiponectin and AdipoR1 expression as well as PPAR gamma transactivation through poly(ADP-ribosyl)ation of PPAR gamma in cultured rat cardiac fibroblasts.
No takes yet. Share an insight, caveat, or question.
Huang et al. (2008) studied this question. Inhibition of PARP-1 (by 3-aminobenzamide, PJ34, or PARP-1 siRNA) vs. Basal conditions was evaluated on Transcription of adiponectin and AdipoR1, and DNA binding/transactivation of PPAR gamma. Inhibition of PARP-1 enhanced DNA binding and transactivation of PPAR gamma, increasing the transcription of adiponectin and AdipoR1 in cultured rat cardiac fibroblasts.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: