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Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling

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Cell Stress and Chaperones Aims and scope

Abstract

The acidic microenvironment around tumor cells is a major determinant in cancer growth, metabolism, and metastasis. However, its role in cancer physiology is still not clearly understood. In the present investigation, an attempt has been made to explore the effect of acidic environment on physiology of cancer cells. Exposure of Raji cells to extracellular acidic environment was associated with enhanced cytosolic calcium level and endoplasmic reticulum stress response. X-box binding protein 1 (XBP1) splicing, CCAAT/enhancer-binding protein homologous protein (CHOP), and glucose-regulated protein 78 kDa (GRP78) upregulation suggested endoplasmic reticulum stress generation. On the other hand, real-time-based upregulation of Bax gene expression and flow cytometric analysis of cytochrome c release as well as enhanced active caspase-3 further confirmed mitochondrion-mediated events leading to induction of apoptosis. The expression of TP53 and p21 was upregulated. These observations collectively strongly suggest that both endoplasmic reticulum stress-mediated calcium release and Bax targeting might be altering mitochondrion membrane potential which in turn could induce secondary apoptotic signals; subsequently, endoplasmic reticulum stress can also lead to nuclear localization of Nuclear factor-κB (NF-κB) which in turn favors p53 mediated apoptotic signals.

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Acknowledgments

This study was supported by the Council of Scientific and Industrial Research (CSIR), New Delhi, India.

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Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Chandigarh, India

    Vishal Sharma & Jagdeep Kaur

  2. Department of Biotechnology, Guru Nanak Dev University, Amritsar, India

    Ramandeep Kaur

  3. Department of Biochemistry, Panjab University, Chandigarh, India

    Archana Bhatnagar

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  1. Vishal Sharma
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  2. Ramandeep Kaur
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  3. Archana Bhatnagar
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  4. Jagdeep Kaur
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Correspondence to Jagdeep Kaur.

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Sharma, V., Kaur, R., Bhatnagar, A. et al. Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling. Cell Stress and Chaperones 20, 431–440 (2015). https://doi.org/10.1007/s12192-014-0568-6

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  • DOI: https://doi.org/10.1007/s12192-014-0568-6

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