Affiliations: Department of Medical Biology and Genetics, Charles
University in Prague, Faculty of Medicine in Hradec Kralove, Simkova 870,
Hradec Kralove I, 500 38, Czech Republic
Note: [] Address for correspondence: Emil Rudolf, Ph.D., Department of
Medical Biology and Genetics, Charles University in Prague, Faculty of Medicine
in Hradec Kralove, Simkova 870, 500 38 Hradec Kralove I, Czech Republic. Tel.:
+420 495816393; Fax: +420 495816495; E-mail: [email protected]
Abstract: Induction of apoptosis by zinc sulfate was investigated during 96 h
exposure on the cancer Hep-2 cell line. During 48 h of exposure, zinc
translocated into mitochondria and stimulated production of reactive oxygen
species (ROS), affected cellular GSH management and induced moderate activation
of p53 and dissipation of mitochondrial membrane potential. In Zn-exposed
cells, mitochondria released cytochrome c and AIF, whose translocation to the
cytoplasm or the nucleus coincided with the activation of apoptosis. The use of
various pharmacological inhibitors inhibiting particular apoptotic targets
(antioxidants such as N-acetyl-cysteine and coenzyme Q, the caspase inhibitors
z-DEVD-fmk and z-VAD-fmk, cyclosporin A and bonkgrekic acid) proved that Zn
acts both directly and indirectly on mitochondria and observed apoptosis is
executed by caspase-dependent and caspase-independent pathways.
Keywords: Zinc, oxidative stress, energy metabolism, mitochondria, apoptosis
Journal: BioFactors, vol. 23, no. 2, pp. 107-120, 2005
