Possible role of interleukin-6 in PC12 cell death induced by MPP+ and tetrahydroisoquinoline.
Interleukin (IL)-6 has been shown to protect neuronal cells from cell death induced by various stimulants. Although neuronal cells including PC12 cells were shown to produce IL-6, little is known about the effects of dopaminergic neurotoxins, 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-4-phenylpyridinium ion (MPP(+)), on IL-6 expression in PC12 cells. In the present study, we investigated the role of IL-6 in the TIQ- and MPP(+)-induced cell death in PC12 cells. Treatment with 3.2 mM TIQ for 24 h caused a delayed cell death (lactate dehydrogenase (LDH) leakage and nuclear DNA fragmentation) markedly 72 h after the addition. Addition of 0.4 mM MPP(+) caused LDH leakage and nuclear DNA fragmentation 24 h after the addition. The cell death induced by MPP(+) was inhibited by an inhibitor of caspases, z-Val-Ala-Asp(OMe)-fluoromethylketone. The cell death induced by TIQ or MPP(+) was inhibited by nerve growth factor and 10% serum and significantly enhanced by the treatment with anti-IL-6 antibody. Both neurotoxins decreased the IL-6 mRNA level in PC12 cells without changing the other tested mRNA levels (IL-1 alpha, beta-actin, etc.). These findings suggest that dopaminergic neurotoxins cause cell death in PC12 cells at least partially by changing IL-6 expression.
Shimma
Naoko
N
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Japan.
Akiyama
Nobuteru
N
Umezawa
Michiko
M
Okuma
Yasunobu
Y
Nomura
Yasuyuki
Y
Saito
Takeshi
T
Horie
Syunji
S
Murayama
Toshihiko
T
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000818:Animals; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044005:Tetrahydroisoquinolines / Q000633:toxicity*; D000093242:Interleukin-6 Inhibitors
D015655:1-Methyl-4-phenylpyridinium; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015850:Interleukin-6; D007770:L-Lactate Dehydrogenase; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D000093242:Interleukin-6 Inhibitors; C476093:z-Val-Ala-Asp(Ome)-fluoromethylketone