Apoptosis

, 11:2167

Effect of aristolochic acid on intracellular calcium concentration and its links with apoptosis in renal tubular cells

  • Yi-Hong Hsin
  • Chi-Hung Cheng
  • Jason T. C. Tzen
  • Ming-Ju Wu
  • Kuo-Hsiung Shu
  • Hong-Chen Chen
Article

DOI: 10.1007/s10495-006-0289-0

Cite this article as:
Hsin, YH., Cheng, CH., Tzen, J.T.C. et al. Apoptosis (2006) 11: 2167. doi:10.1007/s10495-006-0289-0

Abstract

Aristolochic acid (AA) has been demonstrated to play a causal role in Chinese herbs nephropathy. However, the detailed mechanism for AA to induce apoptosis of renal tubular cells remains obscure. In this study, we show that AA evokes a rapid rise in the intracellular Ca2+ concentration of renal tubular cells through release of intracellular endoplasmic reticulum Ca2+ stores and influx of extracellular Ca2+, which in turn causes endoplasmic reticulum stress and mitochondria stress, resulting in activation of caspases and finally apoptosis. Ca2+ antagonists, including calbindin-D28k (an intracellular Ca2+ buffering protein) and BAPTA-AM (a cell-permeable Ca2+ chelator), are capable of ameliorating endoplasmic reticulum stress and mitochondria stress, and thereby enhance the resistance of the cells to AA. Moreover, we show that overexpression of the anti-apoptotic protein Bcl-2 in combination with BAPTA-AM treatment can provide renal tubular cells with almost full protection against AA-induced cytotoxicity. In conclusion, our results demonstrate an impact of AA to intracellular Ca2+ concentration and its link with AA-induced cytotoxicity.

Keywords

Aristolochic acid Apoptosis Calcium ER stress GRP78 Kidney 

Abbreviations

ER

endoplasmic reticulum

GRP

glucose-regulated protein

AA

aristolochic acid

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

BAPTA-AM

1,2-bis(2-aminophenoxy)ethane-N,N,N,N′-tetraacetic acid

ZVAD-fmk

benzyloxycarbonyl-Phe-Val-Ala-Asp (Ome)-fluoromethyl-ketone

MDCK

Madin-Darby canine kidney

COX4

cytochrome oxidase subunit IV

PBS

phosphate-buffered saline

[Ca2+]i

intracellular calcium concentration

PLA2

phospholipase A2

CsA

cyclosporine A

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Yi-Hong Hsin
    • 1
  • Chi-Hung Cheng
    • 2
  • Jason T. C. Tzen
    • 3
  • Ming-Ju Wu
    • 2
  • Kuo-Hsiung Shu
    • 2
  • Hong-Chen Chen
    • 1
  1. 1.Department of Life Science and the Graduate Institute of Biomedical SciencesNational Chung Hsing UniversityTaichungTaiwan
  2. 2.Section of NephrologyTaichung Veterans General HospitalTaichungTaiwan
  3. 3.Graduate Institute of BiotechnologyNational Chung Hsing UniversityTaichungTaiwan

Personalised recommendations