Journal
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
Volume 158, Issue 3, Pages 142-149Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cbpc.2013.07.002
Keywords
Adipokinetic hormone; Calcium channel; Cell signaling; Hydrogen peroxide; Membrane fluidity; Oxidative stress; Protein kinase
Funding
- NSF, EPSCOR [269110-151250]
- Grant Agency of the Czech Republic [P501/10/1215]
- Institute of Entomology [RVO: 60077344]
- GA USB [062/2011/P]
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The involvement of members of the adipokinetic hormone (AKH) family in regulation of response to oxidative stress (OS) has been reported recently. However, despite these neuropeptides being the best studied family of insect hormones, their precise signaling pathways in their OS responsive role remain to be elucidated. In this study, we have used an in vitro assay to determine the importance of extra and intra-cellular Ca2+ stores as well as the involvement of protein kinase C (PKC) and cyclic adenosine 3',5'-monophosphate (cAMP) pathways by which AKH exerts its anti-oxidative effects. Lipid peroxidation product (4-HNE) was significantly enhanced and membrane fluidity reduced in microsomal fractions of isolated brains (CNS) of Pyrrhocoris apterus when treated with hydrogen peroxide (H2O2), whereas these biomarkers of OS were reduced to control levels when H2O2 was co-treated with Pyrap-AKH. The effects of mitigation of OS in isolated CNS by AKH were negated when these treatments were conducted in the presence of Ca2+ channel inhibitors (CdCl2 and thapsigargin). Presence of either bisindolylmaliemide or chelyrythrine chloride (inhibitors of PKC) in the incubating medium also compromised the anti-oxidative function of AKH. However, supplementing the medium with either phorbol myristate acetate (PMA, an activator of PKC) or forskolin (an activator of cAMP) restored the protective effects of exogenous AKH treatment by reducing 4-HNE levels and increasing membrane fluidity to control levels. Taken together, our results strongly implicate the importance of both PKC and cAMP pathways in AKHs' anti-oxidative action by mobilizing both extra and intra-cellular stores of Ca2+. (C) 2013 Elsevier Inc. All rights reserved.
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