Reference - Detail
|Author||Gono T, Takarada T, Fukumori R, Kawaguchi Y, Kaneko H, Hanaoka M, Katsumata Y, Yoneda Y, Yamanaka H.|
|Title||NR2-reactive antibody decreases cell viability through augmentation of Ca(2+) influx in systemic lupus erythematosus.|
OBJECTIVE:Anti-N-methyl-D-aspartate (anti-NMDA) receptor subunit NR2-reactive antibody may play a crucial role in neuronal manifestations of systemic lupus erythematosus (SLE). However, how NR2-reactive antibody acts as a critical modulator of the NMDA receptor is unknown. This study was undertaken to investigate the biologic function of NR2-reactive antibody in patients with SLE.
METHODS:The study included 14 patients with SLE, 9 of whom had NR2-reactive antibody. We analyzed the effects of NR2-reactive antibody on cell viability and intracellular Ca(2+) level. We also investigated the efficacy of zinc as a modulator of the intracellular Ca(2+) level in the presence of NR2-reactive antibody.
RESULTS:There was a significant inverse correlation between the NR2-reactive antibody titer and cell viability (R(2) = 0.67, P < 0.0001; n = 23), and there was a significant association between the NR2-reactive antibody titer and the intracellular Ca(2+) level in NR1/NR2a-transfected HEK 293 cells (R(2) = 0.69, P < 0.0001). Intracellular Ca(2+) levels were significantly higher in cells incubated with IgG derived from NR2-reactive antibody-positive SLE patients than in those incubated with IgG derived from NR2-reactive antibody-negative SLE patients (P = 0.0002). The addition of zinc decreased the intracellular Ca(2+) level in a dose-dependent manner. NR2-reactive antibody-positive SLE IgG weakened the efficacy of zinc as a negative modulator of the intracellular Ca(2+) level.
CONCLUSION:Our findings indicate that NR2-reactive antibody decreases cell viability by Ca(2+) influx in SLE through inhibition of the binding capacity of zinc.
|MeSH||Antibodies / blood Antibodies / pharmacology* Antibodies, Antinuclear / blood Calcium / metabolism* Case-Control Studies Cell Survival / drug effects Cell Survival / physiology DNA / immunology Dose-Response Relationship, Drug HEK293 Cells Humans Immunoglobulin G / pharmacology Kidney / cytology Kidney / drug effects* Kidney / embryology Lupus Erythematosus, Systemic / immunology* Lupus Erythematosus, Systemic / metabolism* Lupus Erythematosus, Systemic / physiopathology Receptors, N-Methyl-D-Aspartate / immunology* Zinc / pharmacology|
|Human and Animal Cells||293(RCB1637)|