1.
Oxidative folding of hepcidin at acidic pH.
Zhang, J, Diamond, S, Arvedson, T, Sasu, BJ, Miranda, LP
Biopolymers. 2010;(2):257-64
Abstract
Hepcidin is a four disulfide 25-residue peptide hormone which has a central role in the regulation of iron homeostasis. To support studies on hepcidin we have sought to establish reliable and robust synthetic methods for the preparation of correctly folded materials. While correctly-folded hepcidin has good aqueous solubility, we have found that its direct synthetic precursor, linear (reduced) hepcidin peptide, is resistant to solubilization, prone to precipitation at pH > or = 6, and thus difficult to fold efficiently. Attempts to directly fold either the crude or purified linear hepcidin peptide by air or DMSO oxidation methods under basic conditions were ineffective. However, addition of a glutathione redox pair system improved folding of purified linear hepcidin at mild basic pH (pH 7.5). Under acidic conditions, it was possible to oxidatively fold both crude and purified hepcidin using a polymer-supported oxidizing strategy. Peptide precipitation was also avoided under acidic conditions. Isolated folding yields of human hepcidin under acidic polymer-assisted conditions were superior to yields under basic folding conditions. These studies enabled identification of a reliable synthetic route for correctly-folded hepcidin.
2.
How does short-term low-dose simvastatin influence serum prohepcidin levels in patients with end-stage renal disease? A pilot study.
Li, XY, Chang, JP, Su, ZW, Li, JH, Peng, BS, Zhu, SL, Cai, AJ, Zhang, J, Jiang, Y
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy. 2010;(3):308-14
Abstract
Anemia is a common clinical problem in end-stage renal disease (ESRD). Despite adequate erythropoiesis-stimulating agent (ESA) supplementation, some ESRD patients still have suboptimal hemoglobin levels, and iron deficiency and inflammation are recognized as the two most common causes. Hepcidin, a newly discovered key regulator of iron homeostasis, is found to be accumulated in ESRD. As it controls iron uptake and release, better reflecting real-time iron demand and availability, hepcidin might become a target in the management of iron deficiency and ESA resistance in dialysis patients. For their pleiotropic functions apart from lipid-modulation, statins are also used as anti-inflammatory or immune-modulating agents. In this study, we applied simvastatin for the purpose of influencing serum prohepcidin level in a group of maintenance hemodialysis patients. Thirty-three ESRD patients undergoing hemodialysis were enrolled and assigned to experimental and hemodialysis control groups according to their lipid profile. Nineteen healthy adults were chosen as a normal control group. The subjects in the experimental group took 20 mg simvastatin orally per night for eight weeks, and those in the hemodialysis control group took no statins or any other lipid-modulating drugs. Before and after the experiment, the serum prohepcidin concentrations, plasma IL-6, and serum C-reactive protein (CRP), ferritin, hemoglobin, albumin, total cholesterol, glycerinate, and LDL and HDL cholesterol levels were determined. Of the 33 hemodialysis patients, the serum prohepcidin concentration was (175.8 +/- 52.9) ng/mL, significantly higher than that in the normal control group (149.5 +/- 24.2) ng/mL (P = 0.048). In the experimental group, the serum prohepcidin level was (156.7 +/- 51.9) ng/mL before treatment, and (190.6 +/- 49.6) ng/mL after eight weeks (P = 0.127). In the hemodialysis control group, the serum prohepcidin level was (190.6 +/- 49.6) ng/mL at the beginning, and (193.5 +/- 36.0) ng/mL after eight weeks (P = 0.728). In the experimental group, after taking simvastatin for eight weeks the serum total cholesterol and triglyceride levels had lowered by 18.6% (P = 0.004) and 55.1% (P = 0.007), respectively. The plasma IL-6, serum CRP, ferritin, hemoglobin, albumin, and LDL and HDL cholesterol levels in both the hemodialysis group remained unchanged. According to our preliminary study, eight weeks of 20 mg simvastatin did not significantly change the serum prohepcidin, high-sensitive CRP, or IL-6 concentrations in the group of maintenance hemodialysis patients.