Redox-Sensitive Calcium/Calmodulin-Dependent Protein Kinase IIα in Angiotensin II Intra-Neuronal Signaling and Hypertension

Authors

Urmi Basu, University of Nebraska Medical Center
Adam J. Case, University of Nebraska Medical CenterFollow
Jinxu Liu, University of Nebraska Medical CenterFollow
Jun Tian, University of Nebraska Medical CenterFollow
Yulong Li, University of Nebraska Medical CenterFollow
Matthew C. Zimmerman, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Redox Biology

Publication Date

2019

Abstract

Dysregulation of brain angiotensin II (AngII) signaling results in modulation of neuronal ion channel activity, an increase in neuronal firing, enhanced sympathoexcitation, and subsequently elevated blood pressure. Studies over the past two decades have shown that these AngII responses are mediated, in part, by reactive oxygen species (ROS). However, the redox-sensitive target(s) that are directly acted upon by these ROS to execute the AngII pathophysiological responses in neurons remain unclear. Calcium/calmodulin-dependent protein kinase II (CaMKII) is an AngII-activated intra-neuronal signaling protein, which has been suggested to be redox sensitive as overexpressing the antioxidant enzyme superoxide dismutase attenuates AngII-induced activation of CaMKII. Herein, we hypothesized that the neuronal isoform of CaMKII, CaMKII-alpha (CaMKIIα), is a redox-sensitive target of AngII, and that mutation of potentially redox-sensitive amino acids in CaMKIIα influences AngII-mediated intra-neuronal signaling and hypertension. Adenoviral vectors expressing wild-type mouse CaMKIIα (Ad.wtCaMKIIα) or mutant CaMKIIα (Ad.mutCaMKIIα) with C280A and M281V mutations were generated to overexpress either CaMKIIα isoform in mouse catecholaminergic cultured neurons (CATH.a) or in the brain subfornical organ (SFO) of hypertensive mice. Overexpressing wtCaMKIIα exacerbated AngII pathophysiological responses as observed by a potentiation of AngII-induced inhibition of voltage-gated K

DOI Link

10.1016/j.redox.2019.101230

ISSN

2213-2317

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Basu, Urmi; Case, Adam J.; Liu, Jinxu; Tian, Jun; Li, Yulong; and Zimmerman, Matthew C., "Redox-Sensitive Calcium/Calmodulin-Dependent Protein Kinase IIα in Angiotensin II Intra-Neuronal Signaling and Hypertension" (2019). Journal Articles: Cellular & Integrative Physiology. 32.
https://digitalcommons.unmc.edu/com_cell_articles/32