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Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells.

Abstract

The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca(2+) stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)).

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  • Authors+Show Affiliations

    ,

    Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

    , , , ,

    Source

    Neurochemistry international 48:8 2006 Jun pg 696-702

    MeSH

    Animals
    Apoptosis
    Calcium
    Calcium Signaling
    Chelating Agents
    Dantrolene
    Endoplasmic Reticulum
    Enzyme Inhibitors
    Fura-2
    Heat-Shock Proteins
    Homeostasis
    Intracellular Fluid
    Lanthanum
    Molecular Chaperones
    Muscle Relaxants, Central
    Nerve Degeneration
    Neurons
    PC12 Cells
    Rats
    Stress, Physiological
    Thapsigargin

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    16481070

    Citation

    Yoshida, Ichiro, et al. "Depletion of Intracellular Ca2+ Store Itself May Be a Major Factor in Thapsigargin-induced ER Stress and Apoptosis in PC12 Cells." Neurochemistry International, vol. 48, no. 8, 2006, pp. 696-702.
    Yoshida I, Monji A, Tashiro K, et al. Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells. Neurochem Int. 2006;48(8):696-702.
    Yoshida, I., Monji, A., Tashiro, K., Nakamura, K., Inoue, R., & Kanba, S. (2006). Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells. Neurochemistry International, 48(8), pp. 696-702.
    Yoshida I, et al. Depletion of Intracellular Ca2+ Store Itself May Be a Major Factor in Thapsigargin-induced ER Stress and Apoptosis in PC12 Cells. Neurochem Int. 2006;48(8):696-702. PubMed PMID: 16481070.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells. AU - Yoshida,Ichiro, AU - Monji,Akira, AU - Tashiro,Ken-ichiro, AU - Nakamura,Kei-ichiro, AU - Inoue,Ryuji, AU - Kanba,Shigenobu, Y1 - 2006/02/14/ PY - 2005/12/13/received PY - 2005/12/13/accepted PY - 2006/2/17/pubmed PY - 2006/7/26/medline PY - 2006/2/17/entrez SP - 696 EP - 702 JF - Neurochemistry international JO - Neurochem. Int. VL - 48 IS - 8 N2 - The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca(2+) stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)). SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/16481070/Depletion_of_intracellular_Ca2+_store_itself_may_be_a_major_factor_in_thapsigargin_induced_ER_stress_and_apoptosis_in_PC12_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(06)00018-0 DB - PRIME DP - Unbound Medicine ER -