search for cellular stress biomarkers in lymphocytes from patients with multiple sclerosis a pilot study寻找细胞压力生物标志物在多发性硬化症患者淋巴细胞从一个试点研究.pdfVIP

Search for Cellular Stress Biomarkers in Lymphocytes from Patients with Multiple Sclerosis: A Pilot Study 1 1 1 2 2 Sabrina Grecchi , Giuliano Mazzini , Antonella Lisa , Marie-Therese Armentero , Roberto Bergamaschi , 2 2 2 1 Alfredo Romani , Fabio Blandini , Carol Di Perri , Anna Ivana Scovassi * 1 IGM-CNR, Pavia, Italy, 2 IRCCS Istituto Neurologico Nazionale C. Mondino, Pavia, Italy Abstract Multiple Sclerosis (MS) is a chronic disease of the central nervous system, the etiology of which, although not completely known, involves inflammation and autoimmunity. In the present study we aimed at identifying molecular markers of apoptosis, cellular stress and DNA damage in isolated peripheral blood mononuclear cells (PBMCs) of MS patients. The analysis was carried on 19 relapsing-remitting untreated MS patients and 13 healthy individuals. We investigated the emergency-driven synthesis of poly(ADP-ribose) (PAR), the expression level of the constitutive enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the DNA damage-induced phosphorylation of histone H2AX. PAR accumulation, PARP-1 and phosphorylated H2AX (cH2AX) were detected by immunofluorescence experiments on PBMCs isolated from 19 patients and 13 healthy volunteers. Our results show for the first time a net increased amount in PAR and cH2AX in MS patients compared to healthy individuals. Patients were further subdivided in three groups, according to the neuroimaging (MRI)- based classification of disease phase. Remarkably, we found a positive correlation between the level of cH2AX and M