PMID- 20842640 OWN - NLM STAT- MEDLINE DCOM- 20110901 LR - 20131121 IS - 1099-1352 (Electronic) IS - 0952-3499 (Linking) VI - 24 IP - 4 DP - 2011 Jul-Aug TI - Diversity of DNA-hydrolyzing antibodies from the sera of autoimmune-prone MRL/MpJ-lpr mice. PG - 557-69 LID - 10.1002/jmr.1067 [doi] AB - It has been shown for the first time that polyclonal IgG abzymes (Abzs) with DNase activity from the sera of autoimmune-prone MRL/MpJ-lpr mice can be separated by isoelectric focusing into many subfractions having the isoelectric points (pI) from 4.5 to 9, with the maximal activity for Abzs with pI = 6.5-9.0. Affinity chromatography on DNA-cellulose separated DNase IgGs into many subfractions demonstrating a range of affinities for DNA and different levels of the relative DNase activities (RDA) due to intrinsically bound metals and after addition of external Mg(2+) , Mn(2+) , Ca(2+), and Mg(2+) +Ca(2+). Some fractions significantly increase RDAs in the presence of external ions (Mg(2+) + Ca(2+) > Mg(2+) > Mn(2+) > Ca(2+)), while each of this cofactor can also inhibit or have no influence on the RDAs of another fractions. It is known that complexes of DNA with histones and other proteins of apoptotic cells are the primary immunogens in systemic lupus erythematosus (SLE). Bovine serum albumin (BSA) and methylated BSA (mBSA) increase the RDAs of only some fractions, while have no effect or inhibit other IgG fractions. The ratio of the RDAs in the presence of all metal ions, BSA, and mBSA was individual for every abzyme fraction. Mn(2+) and Ca(2+) stimulated accumulation of only relaxed form of supercoiled DNA (scDNA) in the case of all subfractions, while in the presence of Mg(2+) antibodies (Abs) of some subfractions (and in the presence of Mn(2+) +Ca(2+) all subfractions) produced relaxed DNA (rDNA) and linear DNA (linDNA) in a variable extent. The data obtained show that the polyclonal Abzs of mice may be a cocktail of Abs directly to DNA, RNA, and their complexes with proteins and anti-idiotypic Abs to active centers of different nucleases. The diversity of the physicochemical and kinetic characteristics of the Abzs seems to be significantly widened when pre-diseased mice spontaneously develop the disease. CI - Copyright (c) 2010 John Wiley & Sons, Ltd. FAU - Kostrikina, Irina A AU - Kostrikina IA AD - Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, pr. Lavrent'eva 8, Novosibirsk 630090, Russia. FAU - Kolesova, Marina E AU - Kolesova ME FAU - Orlovskaya, Irina A AU - Orlovskaya IA FAU - Buneva, Valentina N AU - Buneva VN FAU - Nevinsky, Georgy A AU - Nevinsky GA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100914 PL - England TA - J Mol Recognit JT - Journal of molecular recognition : JMR JID - 9004580 RN - 0 (Antibodies, Catalytic) RN - 0 (DNA-cellulose) RN - 42Z2K6ZL8P (Manganese) RN - 9004-34-6 (Cellulose) RN - 9007-49-2 (DNA) RN - EC 3.1.- (Deoxyribonucleases) RN - I38ZP9992A (Magnesium) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Antibodies, Catalytic/*metabolism MH - Calcium/pharmacology MH - Cattle MH - Cellulose/analogs & derivatives/chemistry MH - Chromatography, Affinity MH - DNA/chemistry/*metabolism MH - Deoxyribonucleases/*metabolism MH - Enzyme Activation/drug effects MH - Isoelectric Focusing MH - Magnesium/pharmacology MH - Manganese/pharmacology MH - Mice MH - Mice, Inbred MRL lpr EDAT- 2010/09/16 06:00 MHDA- 2011/09/02 06:00 CRDT- 2010/09/16 06:00 PHST- 2010/05/12 00:00 [received] PHST- 2010/06/16 00:00 [revised] PHST- 2010/06/17 00:00 [accepted] PHST- 2010/09/16 06:00 [entrez] PHST- 2010/09/16 06:00 [pubmed] PHST- 2011/09/02 06:00 [medline] AID - 10.1002/jmr.1067 [doi] PST - ppublish SO - J Mol Recognit. 2011 Jul-Aug;24(4):557-69. doi: 10.1002/jmr.1067. Epub 2010 Sep 14.