Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca²⁺-Independent Phospholipase A₂ Pathways

The translationally controlled tumor protein (TCTP), initially identified as a tumor- and growth-related protein, is also known as a histamine-releasing factor (HRF). TCTP is widely distributed in the neuronal systems, but its function is largely uncharacterized. Here, we report a novel function of TCTP in the neurotransmitter release from a neurosecretory, pheochromocytoma (PC12) cells. Treatment with recombinant TCTP (rTCTP) enhanced both basal and depolarization (50 mM KCl)-evoked [³H]dopamine release in concentration- and time-dependent manners. Interestingly, even though rTCTP induced the increase in intracellular calcium levels ([Ca²⁺]_i), the rTCTP-driven effect on dopamine release was mediated by a Ca²⁺-independent pathway, as evidenced by the fact that Ca²⁺-modulating agents such as Ca²⁺ chelators and a voltage-gated L-type Ca²⁺-channel blocker did not produce any changes in rTCTP-evoked dopamine release. In a study to investigate the involvement of phospholipase A₂ (PLA₂) in rTCTP-induced dopamine release, the inhibitor for Ca²⁺-independent PLA₂ (iPLA₂) produced a significant inhibitory effect on rTCTP-induced dopamine release, whereas this release was not significantly inhibited by Ca²⁺-dependent cytosolic PLA₂ (cPLA₂) and secretory PLA₂ (sPLA₂) inhibitors. We found that rTCTP-induced dopamine release from neuronal PC12 cells was modulated by a Ca²⁺-independent mechanism that involved PLA₂ in the process, suggesting the regulatory role of TCTP in the neuronal functions.