Poly(ADP-ribose) polymerase 1 inhibition protects against low shear stress induced inflammation

Conclusions: LSS induced oxidative damage and PARP-1 activation via MEK/ERK pathway. PARP-1 inhibition restored Sirt1 activity by increasing NAD+ level and decreased iNOS and ICAM-1 expression by inhibiting NF-κB nuclear translocation and activity as well as NF-κB phosphorylation. PARP-1 played a fundamental role in LSS induced inflammation. Inhibition of PARP-1 might be a mechanism for treatment of inflammation response during atherosclerosis. Highlights ► We firstly demonstrated the critical role of PARP-1 in low shear stress induced inflammation. ► Low shear stress increased superoxide production and nitrotyrosine expression. ► Low shear stress increased PARP-1 expression and PAR formation. ► PARP-1 can be activated by LSS via ERK dependent pathway. ► PARP-1 inhibition decreased LSS-induced inflammatory cytokines upregulation by preventing NF-κB nuclear translocation.
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research