Redox State of Human Serum Albumin in Multiple Sclerosis: A Pilot Study

Abstract

Like in many other pathologies, oxidative stress is involved in the development of neurodegenerative disorders. Human serum albumin (HSA) is the main protein in different body fluids including cerebrospinal fluid (CSF). By its redox state in terms of cysteine-34, albumin serves as marker for oxidative burden. We aimed to evaluate the redox state of HSA in patients with multiple sclerosis in serum and CSF in comparison to controls to identify possible correlations with disease activity and severity. Samples were stored at −70 °C until analysis by HPLC for the determination of albumin redox state in terms of the fractions of human mercaptalbumin (HMA), human nonmercaptalbumin1 (HNA1), and human nonmercaptalbumin2 (HNA2). Albumin in CSF showed significantly higher fractions of the reduced form HMA and decreased HNA1 and HNA2. There was no difference between albumin redox states in serum of patients and controls. In CSF of patients HNA2 showed a trend to higher fractions compared to controls. Albumin redox state in serum was associated with physical disability in remission while albumin redox state in CSF was related to disease activity. Thus, albumin redox state in serum and CSF of patients in relation to disease condition merits further investigation.

The Thiol Group Reactivity and the Antioxidant Property of Human Serum Albumin Are Controlled by the Joint Action of Fatty Acids and Glucose Binding

“…So far, numerous in vivo studies have proved that the content of HSA-SH groups decreased in different pathological conditions compared to the control subjects or those who received some treatment [27,[34][35][36][37]. Contrary to this, there are a few in vivo studies in which HSA-SH group content changes were followed in real time [26], while there are many in vitro studies [5,30].…”

Oxidative Stress Markers in Multiple Sclerosis

“…Table S1 summarizes the results of studies related to markers of oxidative stress in the CSF from MS patients compared to controls [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 ]. Most of these studies found increased CSF levels of markers of lipid peroxidation, such as malonyl-dialdehyde, hydroxyalkenals, diene conjugates, 4-hydroxy-nonenal, oxidized phosphatidylcholine, and isoprostanes in patients diagnosed with MS compared to controls [ 13 , 32 , 33 , 34 , 35 , 37 , 38 , 39 , 40 , 45 , 46 , 47 ], with some exceptions [ 36 ].…”

“…CSF levels of trace metals involved in oxidative stress processes were the subject of a single study, which described increased lead, decreased magnesium, and similar calcium, manganese, and zinc levels in patients with primary progressive MS (PPMS) compared to those with secondary progressive MS (SPMS) and controls [ 51 ]. The CSF human serum albumin (HAS), mercaptoalbumin (HMA), and non-mercaptoalbumins 1 and 2 (HNA1 and HNA2) [ 65 ] levels were reported to be similar in MS patients and controls. CSF neutrophil gelatinase-associated lipocalin (NGAL) was increased [ 39 ] or similar [ 38 ] compared to controls in two studies by the same group.…”

Effect of albumin infusion on oxidative albumin modification and albumin binding capacity in chronic liver failure

“…Albumin was fractionated by high performance liquid chromatography (HPLC) to give three peaks according to Cys-34 in the free sulfhydryl form (HMA), as a mixed disulfide (HNA1), or in a higher oxidation state (HNA2), as previously described. 19 Briefly, 20 μl of diluted plasma were injected into the HPLC system using a Shodex Asahipak ES-502 N 7C anion exchange column (7.5 Â 100 mm, Bartelt Labor-& Datentechnik, Graz, Austria) and 50-mM sodium acetate, 400-mM sodium sulfate, pH 4.85 as mobile phase. For elution, a gradient of 0%-6% ethanol and a flow rate of 1 ml/min were used.…”