D2/D3 receptor agonist ropinirole protects dopaminergic cell line against rotenone-induced apoptosis through inhibition of caspase- and JNK-dependent pathways

Abstract 

Ropinirole, a D2/D3 receptor agonist has been reported to have neuroprotective effects. We showed that ropinirole can prevent rotenone-induced apoptosis in dopaminergic cell line SH-SY5Y through D3 receptor. We found that ropinirole can block the rotenone-induced phosphorylation of JNK, P38 and p-c-Jun, but promote the phosphorylation of ERK1/2. Furthermore, we demonstrated that ropinirole can reduce the rotenone-induced cleavages of caspase 9, caspase 3 and PARP and elevate the expression of anti-apoptotic proteins of p-Akt and bcl-2. These results provide a basis for neuroprotection by this drug for the treatment of Parkinson disease.

Abbreviations: BDNF, brain derived neurotrophic factor, DAT, dopamine transporter, ERK1/2, extracellular-signal regulated kinase 1/2, GDNF, glial-derived neurotrophic factor, JNK, c-Jun NH₂-terminal kinase, MAPK, mitogen-activated protein kinase, PARP, poly [Aop] ribose polymerase, PD, Parkinson disease, SN, substantia nigra

Keywords: Parkinson disease, Rotenone, Apoptosis, Ropinirole, MAP-kinase, SH-SY5Y cell line