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2 results on '"Michiko Umezawa"'

1. Possible Role of Interleukin-6 in PC12 Cell Death Induced by MPP+ and Tetrahydroisoquinoline

Author

Naoko Shimma, Nobuteru Akiyama, Michiko Umezawa, Yasunobu Okuma, Yasuyuki Nomura, Takeshi Saito, Syunji Horie, and Toshihiko Murayama

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

ABSTRACT: 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-1α, β-actin, etc.). These findings suggest that dopaminergic neurotoxins cause cell death in PC12 cells at least partially by changing IL-6 expression.

Published
2003
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2. Inhibition of phospholipase A(2) activity by S-nitroso-cysteine in a cyclic GMP-independent manner in PC12 cells

Author

Siong Heng Thang, Yoshie Yasuda, Yasuyuki Nomura, Michiko Umezawa, and Toshihiko Murayama

Subjects
Wasp Venoms, Ethylmaleimide, Tritium, PC12 Cells, Phospholipases A, Nitric oxide, chemistry.chemical_compound, Phospholipase A2, Cytosol, medicine, Animals, Cysteine, Enzyme Inhibitors, Cyclic GMP, Pharmacology, Phospholipase A, Arachidonic Acid, S-Nitrosothiols, biology, Dose-Response Relationship, Drug, Rats, Enzyme Activation, chemistry, Biochemistry, Mastoparan, biology.protein, Intercellular Signaling Peptides and Proteins, Arachidonic acid, Sodium nitroprusside, Peptides, medicine.drug, Nitroso Compounds
Abstract

Arachidonic acid and nitric oxide (NO) act as retrograde and intercellular messengers in the nervous system. Regulation of cyclooxygenase is well established, but regulation of phospholipase A 2 , the enzyme responsible for the liberation of arachidonic acid, by NO has not been thoroughly investigated. Using the PC12 cell line as a neuronal model, we studied the effects of exogenous NO compounds on arachidonic acid release. Incubation with Ca 2+ ionophores or mastoparan (wasp venom peptide) stimulated [ 3 H]arachidonic acid release from prelabeled PC12 cells. [ 3 H]Arachidonic acid release was inhibited by cytosolic phospholipase A 2 inhibitors, but not by dithiothreitol. A cytosolic phospholipase A 2 protein band with a molecular mass of ∼100 kDa was detected by immunoblotting. S -Nitroso-cysteine inhibited basal and stimulated [ 3 H]arachidonic acid release in concentration-dependent manners. Other NO compounds such as sodium nitroprusside and S -nitroso- N -acetylpenicillamine did not affect [ 3 H]arachidonic acid release. N -Ethylmaleimide also inhibited [ 3 H]arachidonic acid release. The inhibitory effects of S -nitroso-cysteine and N -ethylmaleimide were irreversible, because [ 3 H]arachidonic acid release from PC12 cells preincubated with S -nitroso-cysteine or N -ethylmaleimide was much lower than that from nontreated cells. These findings suggest (a) cytosolic phospholipase A 2 is activated by Ca 2+ or mastoparan, and inhibited by S -nitroso-cysteine in a cyclic GMP-independent manner, (b) N -ethylmaleimide also inhibits cytosolic phospholipase A 2 and arachidonic acid release in PC12 cells. S -Nitroso-cysteine can regulate the production of other retrograde messenger arachidonic acid.

Published
2000

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