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Lanthanum chloride suppresses hydrogen peroxide-enhanced calcification in rat calcifying vascular cells

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Abstract

Lanthanum chloride (LaCl3) has been shown to retard the progression of established atherosclerotic lesions in animal models, and used as a calcium channel blocker in various cellular experiments. In this study, we assessed the role of lanthanum chloride (LaCl3) in H2O2-enhanced calcification in rat calcifying vascular cells (CVCs) and examined the involvement of MAPK signaling pathways. H2O2 induced growth inhibition of CVCs, as well as increases in intracellular levels of calcium and reactive oxygen species, ALP activity, apoptosis and calcium deposition. These effects of H2O2 were suppressed by pretreatment of the cells with 1 μM of LaCl3 for 2 h. In addition, H2O2 activated the phosphorylation of ERK1/2, JNK and p38 MAPK, but only the last two were associated with the ALP activity. Our findings demonstrate that H2O2-enhanced osteoblastic differentiation and apoptosis are responsible for the increased calcification in rat CVCs, and LaCl3 can counteract these effects by suppressing the activation of JNK (JNK2, but not JNK1) and p38 MAPK signaling pathway.

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Acknowledgments

This study was supported by National Natural Science Foundation of China (Grants 20571006 and 20637010), National Basic Research Program of China (Grant 2007CB516806) and Beijing Talent Project.

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Authors and Affiliations

  1. Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, 38 Xueyuan Road, Beijing, 100191, People’s Republic of China

    Yu Shi, Bao-Di Gou, Tian-Lan Zhang & Kui Wang

  2. Department of Chemical Biology, Capital Medical University School of Pharmaceutical Sciences, 10 Xitoutiao, You An Men, Beijing, 100069, People’s Republic of China

    Yan-Ling Shi

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  1. Yu Shi
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Correspondence to Bao-Di Gou or Tian-Lan Zhang.

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Shi, Y., Gou, BD., Shi, YL. et al. Lanthanum chloride suppresses hydrogen peroxide-enhanced calcification in rat calcifying vascular cells. Biometals 22, 317–327 (2009). https://doi.org/10.1007/s10534-008-9168-1

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