Ferrous citrate up-regulates the NOS2 through nuclear translocation of NFκB induced by free radicals generation in mouse cerebral endothelial cells.

Previous studies indicate that the inducible nitric oxide synthase 2 (NOS2) of the brain vascular tissue in experimental subarachnoid hemorrhage (SAH) rats is a critical factor for inducing cerebral vasospasm. However, the underlying molecular mechanisms remain to be elucidated. Here, we applied ferrous citrate (FC) complexes to the primary cultured mouse cerebral endothelial cell (CEC) to mimic the SAH conditions and to address the issue how SAH-induced NOS2 up-regulation.

Inhibition of autophagy as a therapeutic strategy of iron-induced brain injury after hemorrhage.

Premenopausal women have better survival than men after intracerebral hemorrhage, which is associated with iron overproduction and autophagy induction. To examine the participation of neuronal autophagy and estrogen receptor α (ERα) in the E 2-mediated protection, PC12 neurons treated with Atg7 (autophagy-related protein 7) siRNA, rapamycin (an autophagy inducer), or Erα siRNA were applied. To study whether autophagy involves in β-estradiol 3-benzoate (E 2)-mediated neuroprotection against iron-induced striatal injury, castration and E 2 capsule implantation were performed at 2 weeks and 24 h, respectively, before ferrous citrate (FC) infusion into the caudate nucleus (CN) of Sprague Dawley male and female rats.

Methods for studying redox cycling of thioredoxin in mediating preconditioning-induced survival genes and proteins.

Recent advances in molecular biology provide methods and tools for studying cell signaling pathways underlying hormetic mechanisms produced by radiation hormesis, ischemic, remote ischemic, and chemical preconditioning as well as withholding of nutrients and/or trophic factors. Most of the proposed key signaling pathways of hormetic mechanisms remain to be elucidated. For the investigation of possible role of thiol redox signaling systems in hormesis, a serum deprivation preconditioned human cell model, free radical assays, and molecular biological methods are employed for studying whether free radicals, the NO-cGMP-PKG cell signaling pathway, and the redox protein thioredoxin (Trx) play any roles in the hormetic mechanism against cytotoxicity caused by serum deprivation and also neurotoxin 1-methyl-4-phenyltetrahydropyridinium ion (MPP(+)).

Sex-specific role of thioredoxin in neuroprotection against iron-induced brain injury conferred by estradiol.

Background And Purpose: Accumulation of iron after intracerebral hemorrhage causes free radical formation and oxidative damage resulting in liquefaction. The aim of this study was the investigation of molecular mechanisms underlying estrogen-mediated neuroprotective effect against iron-induced brain injury in vivo.

Methods: Age-matched male and female Sprague-Dawley rats were stereotaxically infused with either ferrous citrate (FC) or saline (10 muL) into the right caudate nucleus.