Effects of Paraquat-induced Oxidative Stress on the Neuronal Plasma Membrane Ca2+-ATPase
dc.contributor.author | Zaidi, Asma | |
dc.contributor.author | Fernandes, Denzyl | |
dc.contributor.author | Bean, Jennifer L. | |
dc.contributor.author | Michaelis, Mary Lou | |
dc.date.accessioned | 2017-03-31T20:09:31Z | |
dc.date.available | 2017-03-31T20:09:31Z | |
dc.date.issued | 2009-08-26 | |
dc.identifier.citation | Zaidi, Asma, Denzyl Fernandes, Jennifer L. Bean, and Mary L. Michaelis. "Effects of Paraquat-induced Oxidative Stress on the Neuronal Plasma Membrane Ca2 -ATPase." Free Radical Biology and Medicine 47.10 (2009): 1507-514. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23558 | |
dc.description.abstract | Oxidative stress leads to the disruption of calcium homeostasis in brain neurons; however, the direct effects of oxidants on proteins that regulate intracellular calcium [Ca2+]i are not known. The calmodulin (CaM) -stimulated plasma membrane Ca2+-ATPase (PMCA) plays a critical role in regulating [Ca2+]i. Our previous in vitro studies showed that PMCA present in brain synaptic membranes is readily inactivated by a variety of reactive oxygen species (ROS). The present studies were conducted to determine the vulnerability of PMCA to ROS generated in neurons as would likely occur in vivo. Primary cortical neurons were exposed to paraquat (PQ), a redox cycling agent that generates intracellular ROS. Low concentrations of PQ (5-10 μM) increased PMCA basal activity by 2-fold but abolished its sensitivity to CaM. Higher concentrations (25-100 μM) inhibited both components of PMCA activity. Immunoblots showed the formation of high molecular weight PMCA aggregates. Additionally, PMCA showed evidence of proteolytic degradation. PMCA proteolysis was prevented by a calpain inhibitor, suggesting a role for calpain. Our findings suggest that PMCA is a sensitive target of oxidative stress in primary neurons. Inactivation of this Ca2+ transporter under prolonged oxidative stress could alter neuronal Ca2+ signaling. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/ | |
dc.subject | PMCA | en_US |
dc.subject | Calmodulin | en_US |
dc.subject | Intracellular calcium | en_US |
dc.subject | Oxidative stree | en_US |
dc.subject | Paraquat | en_US |
dc.subject | Superoxide | en_US |
dc.subject | Hydrogen peroxide | en_US |
dc.subject | Calpain | en_US |
dc.title | Effects of Paraquat-induced Oxidative Stress on the Neuronal Plasma Membrane Ca2+-ATPase | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Michaelis, Mary L. | |
kusw.kudepartment | Higuchi Biosciences Center | en_US |
dc.identifier.doi | 10.1016/j.freeradbiomed.2009.08.018 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.rights.accessrights | openAccess |
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Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 (CC BY-NC-ND 3.0 US), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.