Attenuation of Zn 2+ neurotoxicity by aspirin

Role of N-type Ca 2+ 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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Synaptically released Zn 2+ ions enter into neurons primarily through voltage-gated Ca 2+ 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 Zn 2+ neurotoxicity. Administration of 3 to 10 mM aspirin, in cortical cell cultures, attenuated the evolution of neuronal death following exposure to 300 μM Zn 2+ for 30 min. This neuroprotective effect of aspirin was attributable to the prevention of Zn 2+ ion entry. Aspirin interfered with inward currents and an increase in [Ca 2+] i through VGCC and selective binding of ω-conotoxin, sensitive to N-type Ca 2+ channel. The ω-conotoxins GVIA or MVIIC, the selective inhibitors of N-type Ca 2+ channels, attenuated Zn 2+ neurotoxicity. Aspirin derivatives lacking the carboxyl acid group did not reduce Zn 2+ neurotoxicity. The present findings suggest that aspirin prevents Zn 2+-mediated neuronal death by interfering with VGCC, and its action specifically requires the carboxyl acid group.

Original languageEnglish (US)
Pages (from-to)774-783
Number of pages10
JournalNeurobiology of Disease
Volume8
Issue number5
DOIs
StatePublished - 2001
Externally publishedYes

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Aspirin
Acids
Conotoxins
Ions
Neuroprotective Agents
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Cell Culture Techniques
Neurons

ASJC Scopus subject areas

  • Neurology

Cite this

Attenuation of Zn 2+ neurotoxicity by aspirin : Role of N-type Ca 2+ channel and the carboxyl acid group. / Young Kim, Eun; Chang, Su-Youne; Chung, Jun Mo; Rum Ryu, Bo; Joo, Choun Ki; Moon, Ho Sang; Kang, Kyouwarn; Yoon, Sung Hwa; Han, Pyung Lim; Joo Gwag, Byoung.

In: Neurobiology of Disease, Vol. 8, No. 5, 2001, p. 774-783.

Research output: Contribution to journalArticle

Young Kim, E, Chang, S-Y, Chung, JM, Rum Ryu, B, Joo, CK, Moon, HS, Kang, K, Yoon, SH, Han, PL & Joo Gwag, B 2001, 'Attenuation of Zn 2+ neurotoxicity by aspirin: Role of N-type Ca 2+ channel and the carboxyl acid group', Neurobiology of Disease, vol. 8, no. 5, pp. 774-783. https://doi.org/10.1006/nbdi.2001.0421
Young Kim, Eun ; Chang, Su-Youne ; Chung, Jun Mo ; Rum Ryu, Bo ; Joo, Choun Ki ; Moon, Ho Sang ; Kang, Kyouwarn ; Yoon, Sung Hwa ; Han, Pyung Lim ; Joo Gwag, Byoung. / Attenuation of Zn 2+ neurotoxicity by aspirin : Role of N-type Ca 2+ channel and the carboxyl acid group. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 5. pp. 774-783.
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