Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments

Apoptotic cell death is induced in primary hepatocytes by the Ser/Thr protein phosphatase inhibiting cyanobacterial toxin nodularin after only minutes of exposure. Nodularin-induced apoptosis involves a rapid development of reactive oxygen species (ROS), which can be delayed by the Ca2+/calmodulin p...

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Main Authors: Kari E. Fladmark, Therese Solstad, Fiona M. Young, Lise Fismen, Linda V. Hjørnevik
Format: Article
Language:English
Published: MDPI AG 2012-12-01
Series:Toxins
Subjects:
Online Access:http://www.mdpi.com/2072-6651/4/12/1482
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author Kari E. Fladmark
Therese Solstad
Fiona M. Young
Lise Fismen
Linda V. Hjørnevik
author_facet Kari E. Fladmark
Therese Solstad
Fiona M. Young
Lise Fismen
Linda V. Hjørnevik
author_sort Kari E. Fladmark
collection DOAJ
description Apoptotic cell death is induced in primary hepatocytes by the Ser/Thr protein phosphatase inhibiting cyanobacterial toxin nodularin after only minutes of exposure. Nodularin-induced apoptosis involves a rapid development of reactive oxygen species (ROS), which can be delayed by the Ca2+/calmodulin protein kinase II inhibitor KN93. This apoptosis model provides us with a unique population of highly synchronized dying cells, making it possible to identify low abundant phosphoproteins participating in apoptosis signaling. Here, we show that nodularin induces phosphorylation and possibly also cysteine oxidation of the antioxidant Cu,Zn superoxide dismutase (SOD1), without altering enzymatic SOD1 activity. The observed post-translational modifications of SOD1 could be regulated by Ca2+/calmodulin protein kinase II. In untreated hepatocytes, a high concentration of SOD1 was found in the sub-membranous area, co-localized with the cortical actin cytoskeleton. In the early phase of nodularin exposure, SOD1 was found in high concentration in evenly distributed apoptotic buds. Nodularin induced a rapid reorganization of the actin cytoskeleton and, at the time of polarized budding, SOD1 and actin filaments no longer co-localized.
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spelling doaj.art-0c6525aa7ca54977a7ed42eeca8d86df2022-12-22T04:10:31ZengMDPI AGToxins2072-66512012-12-014121482149910.3390/toxins4121482Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin FilamentsKari E. FladmarkTherese SolstadFiona M. YoungLise FismenLinda V. HjørnevikApoptotic cell death is induced in primary hepatocytes by the Ser/Thr protein phosphatase inhibiting cyanobacterial toxin nodularin after only minutes of exposure. Nodularin-induced apoptosis involves a rapid development of reactive oxygen species (ROS), which can be delayed by the Ca2+/calmodulin protein kinase II inhibitor KN93. This apoptosis model provides us with a unique population of highly synchronized dying cells, making it possible to identify low abundant phosphoproteins participating in apoptosis signaling. Here, we show that nodularin induces phosphorylation and possibly also cysteine oxidation of the antioxidant Cu,Zn superoxide dismutase (SOD1), without altering enzymatic SOD1 activity. The observed post-translational modifications of SOD1 could be regulated by Ca2+/calmodulin protein kinase II. In untreated hepatocytes, a high concentration of SOD1 was found in the sub-membranous area, co-localized with the cortical actin cytoskeleton. In the early phase of nodularin exposure, SOD1 was found in high concentration in evenly distributed apoptotic buds. Nodularin induced a rapid reorganization of the actin cytoskeleton and, at the time of polarized budding, SOD1 and actin filaments no longer co-localized.http://www.mdpi.com/2072-6651/4/12/1482nodularinapoptosisSOD1phosphorylationactinROS
spellingShingle Kari E. Fladmark
Therese Solstad
Fiona M. Young
Lise Fismen
Linda V. Hjørnevik
Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments
Toxins
nodularin
apoptosis
SOD1
phosphorylation
actin
ROS
title Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments
title_full Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments
title_fullStr Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments
title_full_unstemmed Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments
title_short Nodularin Exposure Induces SOD1 Phosphorylation and Disrupts SOD1 Co-localization with Actin Filaments
title_sort nodularin exposure induces sod1 phosphorylation and disrupts sod1 co localization with actin filaments
topic nodularin
apoptosis
SOD1
phosphorylation
actin
ROS
url http://www.mdpi.com/2072-6651/4/12/1482
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