Merck
  • Home
  • Search Results
  • Agmatine induces Nrf2 and protects against corticosterone effects in hippocampal neuronal cell line.

Agmatine induces Nrf2 and protects against corticosterone effects in hippocampal neuronal cell line.

Molecular neurobiology (2014-08-03)
Andiara E Freitas, Javier Egea, Izaskun Buendía, Elisa Navarro, Patricia Rada, Antonio Cuadrado, Ana Lúcia S Rodrigues, Manuela G López
ABSTRACT

Hyperactivation of the hypothalamic-pituitary-adrenal axis is a common finding in major depression; this may lead to increased levels of cortisol, which are known to cause oxidative stress imbalance and apoptotic neuronal cell death, particularly in the hippocampus, a key region implicated in mood regulation. Agmatine, an endogenous metabolite of L-arginine, has been proposed for the treatment of major depression. Corticosterone induced apoptotic cell death and increased ROS production in cultured hippocampal neuronal cells, effects that were abolished in a concentration- and time-dependent manner by agmatine. Interestingly, the combination of sub-effective concentrations of agmatine with fluoxetine or imipramine afforded synergic protection. The neuroprotective effect of agmatine was abolished by yohimbine (α2-adrenoceptor antagonist), ketanserin (5-HT2A receptor antagonist), LY294002 (PI3K inhibitor), PD98059 (MEK1/2 inhibitor), SnPP (HO-1 inhibitor), and cycloheximide (protein synthesis inhibitor). Agmatine increased Akt and ERK phosphorylation and induced the transcription factor Nrf2 and the proteins HO-1 and GCLc; induction of these proteins was prevented by yohimbine, ketanserin, LY294002, and PD98059. In conclusion, agmatine affords neuroprotection against corticosterone effects by a mechanism that implicates Nrf2 induction via α2-adrenergic and 5-HT2A receptors, Akt and ERK pathways, and HO-1 and GCLc expression.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Imipramine hydrochloride, BioXtra, ≥99% (TLC)
Sigma-Aldrich
Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, 98%
Sigma-Aldrich
Imipramine hydrochloride, ≥99% (TLC)
Sigma-Aldrich
Yohimbine hydrochloride, ≥98% (HPLC), powder
Sigma-Aldrich
Pindolol, ≥98% (TLC), powder
Sigma-Aldrich
7-Aminoactinomycin D, ~97% (HPLC), powder
Sigma-Aldrich
Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
Sigma-Aldrich
Tin, powder, <150 μm, 99.5% trace metals basis
Sigma-Aldrich
Corticosterone, ≥98.5% (HPLC)
Sigma-Aldrich
Tin, foil, thickness 0.127 mm, 99.9%
Sigma-Aldrich
Tin, granular, 0.425-2.0 mm particle size, ≥99.5%, ACS reagent
Sigma-Aldrich
Tin, powder, 10 μm, 99% trace metals basis
Sigma-Aldrich
Tin, nanopowder, <150 nm particle size (SEM), ≥99% trace metals basis
Sigma-Aldrich
Cycloheximide, Biotechnology Performance Certified
Sigma-Aldrich
Tin, ≥99%, powder
Sigma-Aldrich
2′,7′-Dichlorofluorescein diacetate, BioReagent, suitable for fluorescence, ≥95% (HPLC)
Sigma-Aldrich
Cycloheximide, ≥95% (HPLC)
Sigma-Aldrich
Hydrochloric acid solution, ~6 M in H2O, for amino acid analysis
Supelco
Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
Sigma-Aldrich
Thiazolyl Blue Tetrazolium Bromide, powder, BioReagent, suitable for cell culture, suitable for insect cell culture, ≥97.5% (HPLC)
Sigma-Aldrich
Cycloheximide, from microbial, ≥94% (TLC)
Tin, foil, light tested, 50x50mm, thickness 0.008mm, 99.75%
Tin, foil, not light tested, 150x150mm, thickness 0.007mm, 97.4%
Tin, foil, not light tested, 150x150mm, thickness 0.006mm, 97.4%
Sigma-Aldrich
Hydrogen chloride solution, 3 M in cyclopentyl methyl ether (CPME)
Tin, foil, not light tested, 25x25mm, thickness 0.002mm, temporary acrylic support, 99.75%
Tin, foil, not light tested, 150x150mm, thickness 0.009mm, 97.4%
Tin, foil, not light tested, 25x25mm, thickness 0.006mm, 99.75%
Tin, foil, not light tested, 50x50mm, thickness 0.002mm, temporary acrylic support, 99.75%