The role of Pin1 isomerase on neuronal cell death after focal cerebral ischemic in rats (877.14)

Abstract

Pin1 contains two functional domains, an N‐terminal WW domain and a C‐terminal peptidyl‐prolyl cis/trans isomerase (PPIase) domain. The WW domain is a phosphorylation specific protein interaction module that directs Pin1 to its substrates‐proteins phosphorylated at a certain serine or threonine residue followed by proline (pSer/Thr‐Pro motif). Upon this binding, the PPIase domain catalyzes conformational change of the Pin1 substrates by isomerizing specific pSer/Thr‐Pro bonds. Thus, we hypothesize that Pin1 can regulate neuronal cell death and neurogenesis through Pin1 inhibitor treatment after ischemic brain injury. To test the hypothesis, we elucidated at sub‐acute phases after focal cerebral ischemia to determine the efficacy of Pin1 inhibitor, juglone. Juglone (1mg/kg) was administered once a day during 7 days after focal cerebral ischemia. Histology, protein, and gene analyses were used to determine apoptosis and neurodegeneration at day 7. MCAo+Jug group was significantly led to downregulation of Bcl‐2 and Bax expression on protein level compared to MCAo+Veh group (p<.01). Likewise, juglone treatment was reduced to DAPK1 and Tau5 level on both western blot and immunostaining (p<.01). These results suggest that Pin1 isomerase acts to pro‐apoptotic molecule on ischemic‐induced neuronal cell death after focal cerebral ischemia, as well as Pin1 inhibition might be alleviate to acceleration of apoptotic cell death from acute to subacute after focal cerebral ischemic in rats.Kew words: Focal cerebral ischemia, Pin1, Neuronal cell death.