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자료유형
학술저널
저자정보
Shin, Mi-Kyung (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) Kwon, Yong-Hyun (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) Shin, Jong-Chul (Department of Obstetrics and Gynecology, College of Medicine, Catholic University of Korea) Yang, Dong-Eun (Department of Obstetrics and Gynecology, College of Medicine, Catholic University of Korea) Lee, Sung-Keun (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) Kang, Ju-Hee (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project) Park, Chang-Shin (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
저널정보
대한독성유전단백체학회 Molecular & cellular toxicology Molecular & cellular toxicology 제4권 제1호
발행연도
2008.1
수록면
16 - 21 (6page)

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Cell death of trophoblast, particularly by abnormal release of physiological nitric oxide (NO) has been known to be a causative factor of pre-eclampsia. In the present study, effects of intracellular calcium increase enhancing the activity of NO synthases (neuronal NO synthase, nNOS in this trophoblast cells) on the cell death were examined in a human placental full-term cell line (HT-1). Furthermore, we analyzed the possible mechanisms underlying the augmentation of $Ca^{++}$-mediated NOS activity mediated by protein kinases like PKC, PKA, or CaM-KII. In experiments for cell toxicity, a calcium ionophore (ionomycin $10{\mu}M$) enhanced cell death confirmed by MTT assay, and increased significantly nNOS activity determined with a hemoglobin oxidation assay. This cell death was partially protected by pre-treatment of 7-nitroindazole (7-NI, $10{\mu}M$ and $100{\mu}M$), a nNOS-specific inhibitor. Additionally, $Ca^{++}$-ionophore -induced increase of nNOS activity also was partially normalized by pre-treatment of specific inhibitors of protein kinases, PKC, PKA or CaM-KII. Therefore, we suggest that an increase of calcium influx, leading to the activation of nNOS activity, which in turn may result in the death of trophoblast cells by involvement of signaling mechanisms of protein kinases.

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