Attenuation of Zn2+ neurotoxicity by aspirin: Role of N-type Ca2+ channel and the carboxyl acid group

Eun Young Kim, Su Youne Chang, Jun Mo Chung, Bo Rum Ryu, Choun Ki Joo, Ho Sang Moon, Kyouwarn Kang, Sung Hwa Yoon, Pyung Lim Han, Byoung Joo Gwag

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21 Scopus citations


Synaptically released Zn2+ ions enter into neurons primarily through voltage-gated Ca2+ channels (VGCC) or N-methyl-D-aspartate (NMDA) receptors, which can mediate pathological neuronal death. We studied the possibility (and underlying mechanisms) that aspirin, known to prevent NMDA neurotoxicity, would also attenuate Zn2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical cell cultures, attenuated the evolution of neuronal death following exposure to 300 μM Zn2+ for 30 min. This neuroprotective effect of aspirin was attributable to the prevention of Zn2+ ion entry. Aspirin interfered with inward currents and an increase in [Ca2+]i through VGCC and selective binding of ω-conotoxin, sensitive to N-type Ca2+ channel. The ω-conotoxins GVIA or MVIIC, the selective inhibitors of N-type Ca2+ channels, attenuated Zn2+ neurotoxicity. Aspirin derivatives lacking the carboxyl acid group did not reduce Zn2+ neurotoxicity. The present findings suggest that aspirin prevents Zn2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group.

Original languageEnglish
Pages (from-to)774-783
Number of pages10
JournalNeurobiology of Disease
Issue number5
StatePublished - 2001

Bibliographical note

Funding Information:
This study was supported by a G7 research grant from the ministry of Science and Technology (98-G-08-01-A-07; BJG, SHY, PLH) and in part by the KOSEF grant through the CCSR Fund to J.M.C.


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