Molecular & Cellular Toxicology

The Korean Society of Toxicogenomics and Toxicoproteomics (대한독성유전 단백체학회)
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Neuronal Nitric Oxide-mediated Cytotoxicity in Trophoblast Cells Induced by Increase of Intracellular Calcium

  • 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)
  • Published : 2008.03.31
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Abstract

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.

Keywords

References

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