Functional and dynamic state of inner mitochondrial membrane of sarcoma 37 in mice under administration of sodium dichloroacetate

• Published in: Ukrainian biochemical journal Vol. 86; no. 6; pp. 106 - 118
• Main Authors: Khyzhnyak, S V, Sorokina, L V, Stepanova, L I, Kaplia, A A
• Format: Journal Article
• Language: English
• Published: Ukraine National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry 01-11-2014
• Subjects: Animals; Antimetabolites, Antineoplastic - pharmacology; conformational state of the proteins; Dichloroacetic Acid - pharmacology; Electron Transport - drug effects; glycolysis; Glycolysis - drug effects; inner mitochondrial membrane; Ketone Oxidoreductases - metabolism; Lactic Acid - metabolism; lipid phase microviscosity; Male; Mice; Mice, Inbred BALB C; Mitochondrial Membranes - chemistry; Mitochondrial Membranes - drug effects; Mitochondrial Membranes - metabolism; Muscle Neoplasms - drug therapy; Muscle Neoplasms - metabolism; Muscle Neoplasms - pathology; Neoplasm Transplantation; Protein Conformation; Protein-Serine-Threonine Kinases - metabolism; Proton-Translocating ATPases - metabolism; Reactive Oxygen Species - agonists; Reactive Oxygen Species - metabolism; respiratory chain enzymes; Sarcoma - drug therapy; Sarcoma - metabolism; Sarcoma - pathology; sarcoma 37; sodium dichloroacetate; Tumor Burden - drug effects
• ISSN: 2409-4943; 2413-5003
• DOI: 10.15407/ubj86.06.106

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 H+-ATPase coupled with conformational modification ofprotein molecules and changes of the structural orderliness of the IMM lipid phase, possibly due to intensification of reactive oxygen species generation.