Laboratory for beta-cell biology ****************************************************************************************** * ****************************************************************************************** The long-term research interest of Laboratory for beta-cell biology is focussed on the und molecular mechanisms that are involved in the development of beta-cell dysfunction and typ pathogenesis. Our research aims primarily at the effect of nutrients (particularly saturat unsaturated fatty acids) and persistent organochlorine pollutants (particularly DDT and DD and viability of pancreatic beta-cells. We are also interested in the role of hypoxia as a predisposing factor for the development of beta-cell dysfunction. ****************************************************************************************** * Research in Laboratory for beta-cell biology ****************************************************************************************** The long-term research interest of Laboratory for beta-cell biology aims at the understand mechanisms by which various factors of environment contribute to pancreatic beta-cell dysf pathogenesis of type 2 diabetes. In our recent projects, we are especially interested in t (1) fatty acids, (2) persistent organochlorine pollutants and (3) hypoxia on function and pancreatic beta-cells. 1.Increased level of fatty acids in the blood is considered as one of the main causes of p cell dysfunction and consequent ?-cell death in type 2 diabetes. As we also demonstrated laboratory, increased level of saturated fatty acid species (e.g., palmitate, stearate) cell apoptosis, in contrast to unsaturated fatty acid species (e.g., palmitoleate, oleat significantly less toxic and are even able to inhibit pro-apoptotic effects of saturated Molecular mechanisms of these effects, despite their great therapeutic potential in many medicine, are not clear yet. Employing human pancreatic beta-cell line NES2Y, we have characterized stearate-induced respect to the involvement of various caspases and kinases activation, mitochondrial apo activation and ER stress induction. We found that all pro-apoptotic effects of stearate are inhibited by oleate co-application. In our current research, we aim to reveal the po apoptotic intervention of unsaturated fatty acids into pro-apoptotic signaling exerted b fatty acids. 2.Persistent organochlorine pollutant, e.g., DDT and DDE, despite the prohibition of their country for many years, are still present in the environment and inevitably accumulate i via the food chain. Employing proteomic and other methods, we have revealed several effe DDE on beta-cell function and insulin secretion. Our current research is aimed at elucid molecular mechanisms of these effects with a specific interest focused on a role of vita protein. 3.Hypoxia often accompanies type 2 diabetes due to high coincidence of sleep apnea. Theref interested in the effect of hypoxic conditions on beta-cell viability, including its imp anti-apoptotic potential of saturated and unsaturated fatty acids. ****************************************************************************************** * Personnel ****************************************************************************************** Group leader • RNDr. Vlasta Němcová, Ph.D., e-mail: vlasta.nemcova(zavinac)lf3.cuni.cz [ MAIL "vlasta.nemcova(zavinac)lf3.cuni.cz"] , ORCID: http://orcid.org/0000-0002-2296-3540 [ URL "http://orcid.org/0000-0002-2296-3540" Post-doc • Mgr. Nela Pavlíková, Ph.D. e-mail: nela.pavlikova(zavinac)lf3.cuni.cz [ MAIL "nela.pavlikova(zavinac)lf3.cuni.cz"] , ORCID: https://orcid.org/0000-0001-7468-1505 [ URL "https://orcid.org/0000-0001-7468-150 • RNDr. Jan Šrámek, Ph.D., email: jan.sramek(zavinac)lf3.cuni.cz [ MAIL "jan.sramek(zavinac)lf3.cuni.cz"] , ORCID: https://orcid.org/0000-0003-0218-7238 [ URL "https://orcid.org/0000-0003-0218-723 ****************************************************************************************** * Our recent publications ****************************************************************************************** • Němcová-Fürstová V, Balušíková K, Halada P, Pavlíková N, Šrámek J, Kovář J.: Stearate-in in human pancreatic ?-cells is associated with changes in membrane protein expression an are inhibited by oleate. Proteomics Clin Appl. 2019, doi: 10.1002/prca.201800104. • Jelínek M, Balušíková K, Daniel P, Němcová-Fürstová V, Kirubakaran P, Jaček M, Wei L, Wa J, Ojima I, Kovář J.: Substituents at the C3' and C3'N positions are critical for taxane acquired resistance of cancer cells to paclitaxel. Toxicol Appl Pharmacol. 2018; 347:79- 10.1016/j.taap.2018.04.002. • Brynychova V, Hlavac V, Ehrlichova M, Vaclavikova R, Nemcova-Furstova V, Pecha V, Trnkov Kodet R, Vrana D, Gatek J, Bendova M, Vernerova Z, Kovar J, Soucek P.: Transcript expres variability analysis of caspases in breast carcinomas suggests CASP9 as the most interes Clin Chem Lab Med. 2017; 55(1):111-122. doi: 10.1515/cclm-2016-0271. • Jelinek M, Kabelova A, Sramek J, Seitz J, Ojima I, Kovar J.: Differing Mechanisms of Dea by Fluorinated Taxane SB-T-12854 in Breast Cancer Cells. Anticancer Res. 2017; 37(4):158 10.21873/anticanres.11488 • Šrámek J, Němcová-Fürstová V, Pavlíková N, Kovář J.: Effect of Saturated Stearic Acid on and ER Stress Signaling Pathways during Apoptosis Induction in Human Pancreatic ?-Cells Unsaturated Oleic Acid. Int J Mol Sci. 2017; 18(11). pii: E2313. doi: 10.3390/ijms181123 • Brynychova V, Ehrlichova M, Hlavac V, Nemcova-Furstova V, Pecha V, Leva J, Trnkova M, Mr Kodet R, Vrana D, Kovar J, Vaclavikova R, Gut I, Soucek P.: Genetic and functional analy explain the association of high PRC1 expression with poor survival of breast carcinoma p Pharmacother. 2016; 83:857-864. doi: 10.1016/j.biopha.2016.07.047. • Němcová-Fürstová V, Kopperová D, Balušíková K, Ehrlichová M, Brynychová V, Václavíková R P, Souček P, Kovář J.: Characterization of acquired paclitaxel resistance of breast canc and involvement of ABC transporters. Toxicol Appl Pharmacol. 2016; 310:215-228. doi: 10. j.taap.2016.09.020. • Šrámek J, Němcová-Fürstová V, Kovář J.: Kinase Signaling in Apoptosis Induced by Saturat in Pancreatic ?-Cells. Int J Mol Sci. 2016; 17(9). pii: E1400. doi: 10.3390/ijms17091400 • Šrámek J, Němcová-Fürstová V, Balušíková K, Daniel P, Jelínek M, James RF, Kovář J.: 38 Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Aci Pancreatic ?-Cells. Int J Mol Sci. 2016; 17(2):159. doi: 10.3390/ijms17020159. • Weiszenstein M, Pavlikova N, Elkalaf M, Halada P, Seda O, Trnka J, Kovar J, Polak J.: Th of Pericellular Oxygen Levels on Proteomic Profile and Lipogenesis in 3T3-L1 Differentia Preadipocytes Cultured on Gas-Permeable Cultureware. PLoS One. 2016; 29;11(3):e0152382. journal.pone.0152382. • Jiroutková K, Krajčová A, Ziak J, Fric M, Waldauf P, Džupa V, Gojda J, Němcova-Fürstová Elkalaf M, Trnka J, Duška F.: Mitochondrial function in skeletal muscle of patients with critical illness and ICU-acquired weakness. Crit Care. 2015; 19:448. doi: 10.1186/s13054 • Jelínek M, Balušíková K, Schmiedlová M, Němcová-Fürstová V, Šrámek J, Stančíková J, Zana I, Kovář J.: The role of individual caspases in cell death induction by taxanes in breas Cancer Cell Int. 2015; 15(1):8. doi: 10.1186/s12935-015-0155-7. • Pavlikova N, Weiszenstein M, Pala J, Halada P, Seda O, Elkalaf M, Trnka J, Kovar J, Pola of cultureware surfaces on functional and structural components of differentiated 3T3-L1 Cell Mol Biol Lett. 2015; 20(5):919-36. doi: 10.1515/cmble-2015-0054. • Pavlikova N, Smetana P, Halada P, Kovar J.: Effect of prolonged exposure to sublethal co DDT and DDE on protein expression in human pancreatic beta cells. Environ Res. 2015; 142 10.1016/j.envres.2015.06.046. • Pavlikova N, Bartonova I, Dincakova L, Halada P, Kovar J.: Differentially expressed prot breast cancer cells sensitive and resistant to paclitaxel. Int J Oncol. 2014; 45(2):822- 10.3892/ijo.2014.2484. • Jelínek M, Balušíková K, Kopperová D, N?mcová-Fürstová V, Šrámek J, Fidlerová J, Zanardi Kovář J.: Caspase-2 is involved in cell death induction by taxanes in breast cancer cell Int. 2013 ; 13(1):42. doi: 10.1186/1475-2867-13-42. • Němcová-Fürstová V, Balušíková K, Srámek J, James RF, Kovář J.: Caspase-2 and JNK activa fatty acids are not involved in apoptosis induction but modulate ER stress in human panc Cell Physiol Biochem. 2013; 31(2-3):277-89. doi: 10.1159/000343367.