Abstract
Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH) and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothesis and demonstrated that ad-hepcidin and hepcidin peptide both have the ability to suppress the hemin-induced increase in LDH release and apoptotic cell numbers, to reduce cell iron and ferritin contents, and to inhibit expression of transferrin receptor 1, divalent metal transporter 1, and ferroportin 1 in hemin-treated neurons. We conclude that hepcidin protects neuron from hemin-mediated injury by reducing iron via inhibition of expression of iron transport proteins.
Highlights
Intracerebral hemorrhage (ICH) is a major public health problem (van Asch et al, 2010) and affects more than one million people worldwide annually (Liu et al, 2007; Anderson et al, 2013)
Infection of the cells with ad-blank had no effect on the expression of hepcidin mRNA, no difference being found between the neurons in Ad-Blank and control groups (Figure 1)
We investigated the effects of different concentrations of ad-hepcidin on neuronal integrity or viability by incubating cultured neurons with 0, 25, 50, 100, and 200 MOI of adhepcidin for 40-h respectively and examining the contents of Lactate dehydrogenase (LDH) release from neurons
Summary
Intracerebral hemorrhage (ICH) is a major public health problem (van Asch et al, 2010) and affects more than one million people worldwide annually (Liu et al, 2007; Anderson et al, 2013). A breakdown product of hemoglobin, plays a key role in mediating secondary neuronal injury after ICH (Qureshi et al, 2009; Babu et al, 2012; Owen et al, 2016). It has been reported that slowing iron release by inhibiting hemin breakdown could induce a decrease in cell death and reactive oxygen species (Chang et al, 2011; Chen-Roetling et al, 2014) The studies have showed that the iron chelator including Deferoxamine Mesylate (DFO) reduces hemin and iron-mediated neurotoxicity, perihematoma edema, and neuronal damage, leading to good neurologic outcomes after ICH (Hoepken et al, 2004; Nakamura et al, 2004; Masuda et al, 2007; Belur et al, 2013; Yeatts et al, 2013).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
