Department of Biochemistry
Head: Prof. Maria Jolanta RĘDOWICZ
e-mail: j.redowicz@nencki.gov.pl
The Department of Biochemistry consists of nine laboratories. The research projects carried out in the Department are focused on molecular regulation of cell fate and physiology under normal and pathological conditions.
We are interested in delineating signaling pathways responsible for cell stress, death and senescence as well as lipid metabolism in normal and pathological conditions. The mechanisms of the protective action of potassium channel openers on cardiac and skeletal muscle mitochondria are also a subject of the studies, as they can have serious application in protecting against heart damage. Projects aimed at novel approaches to old targets in chemotherapy are focused on thymidylate synthase post-translational modifications and capacity to bind RNA and suppress translation. In particular, attention is paid to the role of mitochondria in cellular stress, apoptosis and calcium homeostasis with an emphasis on various calcium-binding proteins. Mammalian annexins, their structure, function and role in human diseases, in which membrane permeability to ions and vesicular transport are affected, are also investigated. The studies on motile systems are mainly focused on structure-function relationships of molecular motors (kinesins and myosins), cytoskeletal and adaptor proteins. Functional interaction of prions with the microtubular system is also studied. The molecular mechanisms of lipotoxicity with special emphasis on lipid-induced insulin resistance, the role of fatty acids in the regulation of gene expression and energy metabolism and new perspective therapy for diabetes are also fields of our research.
Major recent achievements of the laboratories include:
• characteristics of participation of annexins in tissue mineralization, secretion of catecholamines, and transport and storage of cholesterol in Niemann-Pick type C disease (Head of Laboratory – Sławomir Pikuła)
• further elucidation of the mechanism of cellular stress and a role of interactions between mitochondria, the plasma membrane and the endoplasmic reticulum under normal and pathological conditions in mammalian cells (Head of Laboratory – Jerzy Duszyński)
• finding of high expression of enzymes involved in thymidylate biosynthesis in developmentally arrested larvae of parasitic (Trichinella spiralis and T. pseudospiralis) and free-living (Caenorhabditis elegans) nematodes, suggest- ing global cell cycle arrest (Head of Laboratory – Wojciech Rode)
• elucidation of the molecular mechanisms of mitotic catastrophe and cellular senescence as a cell fate of cancer cells resistant to apoptosis induced by many factors and demonstrating that curcumin, a natural dye, is a potent inducer of these processes (Head of Laboratory – Ewa Sikora)
• identification of new potassium channels in the inner mitochondrial membrane (Head of Laboratory – Adam Szewczyk)
• identification of nucleotide receptors participating in the impaired calcium homeostasis in dystrophic mouse myoblasts (Head of Laboratory – Krzysztof Zabłocki)
• establishing the role of stearoyl-CoA desaturase in regula- tion of cardiac substrate utilization and of muscle insulin sensitivity (Head of Laboratory – Agnieszka Dobrzyń).
• production and purification of a heterodimeric kinesin Ncd, in which each of the subunits can be independently genetically manipulated (Head of Laboratory – Andrzej Kasprzak).
• characterization of the effects of prion protein on micro- tubule formation and proteomic analysis of Ruk/CIN85 binding-partners and functional implications of translo- cation of myosin VI into the nucleus (Head of Laboratory – Maria Jolanta Rędowicz)
The field of expertise of members of the Department is powered by many experimental units accessible within the Department or in the Institute core facility laboratories, described in the relevant sections within this issue.
Selected publications of the Department:
Jarmuła A., Cieplak P., Krygowski T.M., Rode W. (2007) The effect of 5-substitution in the pyrimidine ring of dump on the interaction with thymidylate synthase: Molecular modeling and QSAR. Bioorg. Med. Chem. 15: 2346-2358
Kicińska A., Swida A., Bednarczyk P., Koszela-Piotrowska I., Choma K., Dołowy K., Szewczyk A., Jarmuszkiewicz W. (2007) ATP-sensitive potassium channel in mitochondria of the eukaryotic microorganism Acanthamoeba castellanii. J. Biol. Chem. 282: 17433-17441
Schönfeld P., Wojtczak L. (2007) Fatty acids decrease mitochondrial generation of reactive oxygen species at the reverse electron transport but increase it at the forward transport. Biochim Biophys Acta 1767: 1032-1040
Sobczak M., Kocik E., Rędowicz M.J. (2007) A novel Amoeba proteus 120-kDa actin-binding protein with only one filamin repeat and a coiled-coil region. Biochem. Cell Biol. 85: 22-31
Kirilenko A., Pikuła S., Bandorowicz-Pikuła J. (2006) Effects of mutagenesis of W343 in human annexin A6 isoform 1 on its interaction with GTP: nucleotide-induced oligomer formation and ion channel activity. Biochemistry 45: 4965-4973
Reuther C., Hajdo Ł., Tucker R., Kasprzak A. A., Diez S. (2006) Biotemplated nanopatterning of planar surfaces with molecular motors. Nano Lett. 6: 2177-2183
Sikora E., Bielak-Zmijewska A., Magalska A., Piwocka K., Mosieniak G., Kalinowska M., Widlak P., Cymerman I. A., Bujnicki J.M. (2006) Curcumin induces caspase-3-dependent apoptotic pathway but inhibits DNA fragmentation factor 40/caspase-activated DNase endonuclease in human Jurkat cells. Mol. Cancer Ther. 5: 927-934
Yeung D., Zabłocki K., Jiang T., Arkle S., Brutkowski W., Brown J., Lochmuller H., Simon J., Barnard E.A., Górecki D.C. (2006) Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cell. FASEB J. 20: 610-620
Wawro B., Khaitlina S. Y., Galińska-Rakoczy A., Strzelecka-Gołaszewska H. (2005) Role of actin DNase-I-binding loop in myosin subfragment 1-induced polymerization of G-actin. Implications to the polymerization mechanism. Biophys. J. 88: 2883-2896
Zabłocki K., Szczepanowska J., Duszyński J. (2005) Extracellular pH modifies mitochondrial control of capacitative calcium entry in Jurkat cells. J. Biol. Chem. 280: 3516-3521
Zhang L., Balcerzak M., Radisson J., Thouverey C., Pikuła S., Azzar G., Buchet R. (2005) Phosphodiesterase activity of alkaline phosphatase in ATP-initiated Ca2+ and phosphate deposition in isolated chicken matrix vesicles. J. Biol. Chem. 280: 37289-37296
