Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury.

  • Authors:
    • Kei Yamamoto
    • Naruya Tomita
    • Shin-ichi Yoshimura
    • Hironori Nakagami
    • Yoshiaki Taniyama
    • Keita Yamasaki
    • Toshio Ogihara
    • Ryuichi Morishita
  • View Affiliations

  • Published online on: October 1, 2004     https://doi.org/10.3892/ijmm.14.4.633
  • Pages: 633-673
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Abstract

Although injury of epithelial cells has been reported to be responsible for renal disease such as acute renal failure, its molecular mechanisms are largely unknown. As hypoxia has been postulated as the initial trigger of epithelial injury, we studied the molecular mechanisms of apoptosis induced by hypoxia in human renal epithelial cells. Severe hypoxia caused epithelial cell death, accompanied by a significant increase in LDH release (p<0.01). In addition, hypoxic treatment of epithelial cells resulted in a significant increase in apoptotic cells as assessed by cell morphology (p<0.01). The apoptotic change in epithelial cells under hypoxic condition was also confirmed by a significant increase in caspase-3-like activity and release of cytochrome c (p<0.01). The decrease in epithelial cell number was completely abolished by addition of a wide-spectrum caspase inhibitor, Z-VAD, rather than Z-DEVD, a specific caspase-3 inhibitor (p<0.01). Thus, we further studied the molecular mechanisms of apoptosis induced by hypoxia. Anti-apoptotic factors, Bcl-2 and Bcl-xL, were significantly decreased in epithelial cells under a hypoxic condition as assessed by Western blotting (p<0.01). In contrast, hypoxia did not alter their location. Of particular importance, translocation of a proapoptotic factor, Bax, from the cytoplasm to the mitochondrial membrane was observed in response to hypoxia, whereas total Bax protein was not changed by hypoxia. Overall, this study demonstrated that hypoxia caused epithelial cell death induced by caspase-3-like activity-dependent apoptosis. The pro-apoptotic mechanisms of hypoxia in epithelial cells largely depend on a significant decrease in Bcl-2 and Bcl-xL. In addition, the present results demonstrate that translocation of Bax from the cytosol to the mitochondrial membrane occurred under hypoxia, thereby leading to pathological tissue destruction.

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October 2004
Volume 14 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Yamamoto K, Tomita N, Yoshimura S, Nakagami H, Taniyama Y, Yamasaki K, Ogihara T and Morishita R: Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury.. Int J Mol Med 14: 633-673, 2004
APA
Yamamoto, K., Tomita, N., Yoshimura, S., Nakagami, H., Taniyama, Y., Yamasaki, K. ... Morishita, R. (2004). Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury.. International Journal of Molecular Medicine, 14, 633-673. https://doi.org/10.3892/ijmm.14.4.633
MLA
Yamamoto, K., Tomita, N., Yoshimura, S., Nakagami, H., Taniyama, Y., Yamasaki, K., Ogihara, T., Morishita, R."Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury.". International Journal of Molecular Medicine 14.4 (2004): 633-673.
Chicago
Yamamoto, K., Tomita, N., Yoshimura, S., Nakagami, H., Taniyama, Y., Yamasaki, K., Ogihara, T., Morishita, R."Hypoxia-induced renal epithelial cell death through caspase-dependent pathway: role of Bcl-2, Bcl-xL and Bax in tubular injury.". International Journal of Molecular Medicine 14, no. 4 (2004): 633-673. https://doi.org/10.3892/ijmm.14.4.633