Tag Archives: glycolysis
Scientific and practical activity of the Department of Molecular Biology of the Palladin Institute of Biochemistry of NAS of Ukraine
R. P. Vynogradova, M. V. Grigorieva, V. M. Danilova
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: valdan@biochem.kiev.ua
The present paper gives a detailed analysis of scientific and practical activity of the Department of Molecular Biology of the Palladin Institute of Biochemistry of NAS of Ukraine in the context of the history of its development. The most important results of the research of molecular mechanisms of regulation of glycolysis and gene expression in malignant tumors upon hypoxia; identification of key transcription factors of the regulation of proliferation and the role of alternative splicing in the regulation of the activity of the different PFKFB isoforms are reported. In recent years, the efforts of the department’s staff have been focused on studying the role of endoplasmic reticulum stress and the regulation of metabolism and proliferation processes at the level of gene expression in genome reprogramming. The obtained results allow to establish the molecular bases of pathogenesis of various diseases and to develop new effective methods for their diagnosis, prevention and treatment.
Endoplasmic reticulum stress, its sensor and signalling systems and the role in regulation of gene expression at malignant tumor growth and hypoxia
O. H. Minchenko, A. P. Kharkova, T. V. Bakalets, I. V. Kryvdiuk
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: ominchenko@yahoo.com
Hypoxia is one of the inductors of the expression of a large group of genes, which control glycolysis and proliferation processes in low oxygen conditions or as a result of low oxygen consumption. Moreover, hypoxia is one of the factors which induce the endoplasmic reticulum stress which, like hypoxia, is an obligatory component of malignant tumor growth and is connected with cytoplasm and nuclei through three sensor and signalling systems: PERK, ATF6 та ERN1. The suppression of ERN1, the main sensing and signalling enzyme of endoplasmic reticulum stress, leads to a decrease of tumor growth and changes the character of hypoxic regulation of many genes responsible for the control of proliferation and glycolysis. ERN1 sensing and signalling system controls the expression of a large set of genes, which are dependent on endoplasmic reticulum stress as well as hypoxia. Moreover, this signalling pathway is an important factor of malignant tumor growth.
Functional and dynamic state of inner mitochondrial membrane of sarcoma 37 in mice under administration of sodium dichloroacetate
S. V. Khyzhnyak1, L. V. Sorokina2, L. I. Stepanova3, A. A. Kaplia4
1National University of Life and Environmental Sciences of Ukraine, Kyiv;
e-mail: khs2014@ukr.net;
2R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
3ESC “Institute of Biology”, Taras Shevchenko National University of Kyiv, Ukraine;
4Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv
The activity of enzymes of the respiratory chain and structural-dynamic properties of the inner mitochondrial membrane (IMM) of sarcoma 37 (S37) in mice under sodium dichloroacetate (SDA) administration in a daily dose of 86 mg/kg of body weight starting from the 2nd day after tumor transplantation were investigated. The dynamic and structural state of the IMM components was determined using the fluorescent probes. With S37 growth the intensification of glycolytic metabolism occurred on the background of suppressed functional capacity of mitochondrial respiratory chain enzymes. The changes of conformational properties of protein molecules and the increase of IMM lipid phase microviscosity were shown. The administration of SDA promotes the decrease of lactate content and the increase of pyruvate dehydrogenase activity in S37. This was accompanied by further suppression of the functional activity of the respiratory chain complexes and Н+-АТРase coupled with conformational modification of protein molecules and changes of the structural orderliness of the IMM lipid phase, possibly due to intensification of reactive oxygen species generation.