Pyrroloquinoline Quinone Prevents Oxidative Stress-induced Neuronal Death Probably Through Changes in Oxidative Status of DJ-1

Pyrroloquinoline quinone (PQQ) has been shown to play a role as an anti-oxidant in neuronal cells and prevent neuronal cell death in a rodent stroke model. DJ-1, a causative gene product for a familial form of Parkinson's disease, plays a role in anti-oxidative stress function by self-oxidation of DJ-1. In this study, the expression level and oxidation status of DJ-1 were examined in SHSY-5Y cells and primary cultured neurons treated with 6-hydroxydopamine (6-OHDA) or H(2)O(2) in the presence or absence of PQQ. The pI shift of DJ-1 to an acidic point, which was observed in SHSY-5Y cells treated with 6-OHDA, was inhibited by PQQ. TOF-MS analyses showed that while the level of a reduced form of DJ-1, one of the active forms of DJ-1, was decreased in SHSY-5Y cells treated with 6-OHDA or H(2)O(2), PQQ increased the level of the reduced form of DJ-1. These results suggest that PQQ prevents oxidative stress-induced changes in oxidative status of DJ-1. Therefore, the neuroprotective effects of PQQ on oxidative stress-induced neuronal death may be at least in part involved in increased level of an active form of DJ-1.