title: Translationally Controlled Tumor Protein Stimulates Dopamine Release from PC12 Cells via Ca2+-Independent Phospholipase A₂ Pathways.
abstract: 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.
authors: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. hui7505@hanmail.net.
authors: Jihui
authors: J
authors: Seo
authors: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. jhmaeng@ewha.ac.kr.
authors: Jeehye
authors: J
authors: Maeng
authors: College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea. hjkim@ewha.ac.kr.
authors: Hwa-Jung
authors: HJ
authors: Kim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D054501:Group II Phospholipases A2 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; C000715649:Tpt1 protein, rat; D000090324:Tumor Protein, Translationally-Controlled 1; D054501:Group II Phospholipases A2; D054510:Phospholipases A2, Cytosolic; D002118:Calcium; D004298:Dopamine
keywords: Ca2+-independent pathways; PC12 neuronal cells; dopamine release; histamine releasing factor; phospholipase A2; translationally controlled tumor protein