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Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes.
J Neurosci. 2000 Dec 01; 20(23):RC111.JN

Abstract

Zinc overload may be a key mechanism of neuronal death in acute brain injury. We have demonstrated previously that zinc overload neurotoxicity involves protein kinase C (PKC)-dependent rises in intracellular levels of reactive oxygen species (ROS). However, the cascade linking PKC activation to ROS generation in cultured cortical neurons has been unknown. A recent study has demonstrated that ROS-generating NADPH oxidase is present in sympathetic neurons and contributes to NGF deprivation-induced cell death. Because NADPH oxidase is activated by PKC, in the present study, we examined the possibility that NADPH oxidase is the effector for oxidative stress in zinc-overloaded cortical cells. Reverse transcription-PCR and Western blot analyses revealed that naive cultured cortical cells express subunits of NADPH oxidase at low levels. Exposure to zinc substantially increased levels of NADPH oxidase subunits in both neurons and astrocytes. In addition, zinc exposure induced translocation of the p47(PHOX) and p67(PHOX) subunits to the membrane, a signature event for NADPH oxidase activation. Addition of a selective PKC inhibitor, GF109203X, blocked both the induction and the membrane translocation of NADPH oxidase by zinc. Supporting the role for NADPH oxidase in zinc-triggered oxidative injury, NADPH oxidase inhibitors attenuated ROS production and cortical neuronal death induced by zinc. In addition, Cu/Zn-superoxide dismutase and catalase attenuated zinc-induced cortical neuronal death. Our results have demonstrated that zinc overload induces and activates NADPH oxidase in cortical neurons and astrocytes in a PKC-dependent manner. Thus, NADPH oxidase may be an enzyme contributing to ROS generation in zinc-overloaded cortical neurons and astrocytes.

Authors+Show Affiliations

National Creative Research Initiative Center for the Study of CNS Zinc and Department of Neurology, University of Ulsan College of Medicine, Seoul 138-736, Korea.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11090611

Citation

Noh, K M., and J Y. Koh. "Induction and Activation By Zinc of NADPH Oxidase in Cultured Cortical Neurons and Astrocytes." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 20, no. 23, 2000, pp. RC111.
Noh KM, Koh JY. Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. J Neurosci. 2000;20(23):RC111.
Noh, K. M., & Koh, J. Y. (2000). Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 20(23), RC111.
Noh KM, Koh JY. Induction and Activation By Zinc of NADPH Oxidase in Cultured Cortical Neurons and Astrocytes. J Neurosci. 2000 Dec 1;20(23):RC111. PubMed PMID: 11090611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. AU - Noh,K M, AU - Koh,J Y, PY - 2000/11/25/pubmed PY - 2001/3/3/medline PY - 2000/11/25/entrez SP - RC111 EP - RC111 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 20 IS - 23 N2 - Zinc overload may be a key mechanism of neuronal death in acute brain injury. We have demonstrated previously that zinc overload neurotoxicity involves protein kinase C (PKC)-dependent rises in intracellular levels of reactive oxygen species (ROS). However, the cascade linking PKC activation to ROS generation in cultured cortical neurons has been unknown. A recent study has demonstrated that ROS-generating NADPH oxidase is present in sympathetic neurons and contributes to NGF deprivation-induced cell death. Because NADPH oxidase is activated by PKC, in the present study, we examined the possibility that NADPH oxidase is the effector for oxidative stress in zinc-overloaded cortical cells. Reverse transcription-PCR and Western blot analyses revealed that naive cultured cortical cells express subunits of NADPH oxidase at low levels. Exposure to zinc substantially increased levels of NADPH oxidase subunits in both neurons and astrocytes. In addition, zinc exposure induced translocation of the p47(PHOX) and p67(PHOX) subunits to the membrane, a signature event for NADPH oxidase activation. Addition of a selective PKC inhibitor, GF109203X, blocked both the induction and the membrane translocation of NADPH oxidase by zinc. Supporting the role for NADPH oxidase in zinc-triggered oxidative injury, NADPH oxidase inhibitors attenuated ROS production and cortical neuronal death induced by zinc. In addition, Cu/Zn-superoxide dismutase and catalase attenuated zinc-induced cortical neuronal death. Our results have demonstrated that zinc overload induces and activates NADPH oxidase in cortical neurons and astrocytes in a PKC-dependent manner. Thus, NADPH oxidase may be an enzyme contributing to ROS generation in zinc-overloaded cortical neurons and astrocytes. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11090611/Induction_and_activation_by_zinc_of_NADPH_oxidase_in_cultured_cortical_neurons_and_astrocytes_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11090611 DB - PRIME DP - Unbound Medicine ER -