Respondent
Theme
Peculiarities of bioenergetic processes in mitochondria of Nemeth-Kelner lymphoma cells.
Defence Date
Annotation
Thesis for PhD degree in Biology, specialty 03.00.13 – Human and Animal
Physiology. – Ivan Franko National University of Lviv, Lviv, 2016.
The peculiarities of bioenergetic processes in mitochondria of Nemeth-Kelner
lymphoma cells (NK/Ly) have been investigated using polarographic method. For the first
time the functionally active mitochondria of NK/Ly with coupled respiration and ATP
synthesis were isolated. Oxygen uptake and rate of ADP oxidative phosphorylation in
lymphoma mitochondria are clearly lower compared to equal parameters in both mouse
and rat liver mitochondria.
Mitochondrial suspension isolated from lymphoma and hepatic cells have been
proposed to use as a target of anticancer drugs in tumor and normal cells. The well-known
anti-tumor drug doxorubicin decreases the rate of respiration in the mitochondria of mouse
lymphoma by 43.8%, but does not affect the coupling processes of respiration and
oxidative phosphorylation. Newly developed drug Les 3506 show reducing effect on
normal liver mitochondria decreasing both the rate of oxygen uptake by 36.1% in the State
3 (according to B. Chance) and rate of phosphorylation by 40.7%.
To compare effects of anti-tumor drug on both lymphoma and liver mitochondria an
antibiotic landomycine A has been used. This treatment reduces metabolic rate of
respiration in State 3 in liver and lymphoma mitochondria and rate of oxidative
phosphorylation in liver mitochondria when NAD-dependent substrate α-ketoglutarate is
used.
Bafilomicyne and NAADP lead to a decrease in metabolic rate in State 3 by 49.1%
(bafilomicyne) and by 67.1% (NAADP) in lymphoma mitochondria without significant
affect on liver mitochondria. Bafilomicyne with NAADP leads to complete uncoupling
lymphoma mitochondria after (during) the synthesis of ATP in oxidation of α-
ketoglutarate and succinate. Using the experimental lymphoma NK/Ly model it has been
shown that polarography of isolated mitochondria can be used as a effective tool for study
both peculiarities of tumor cellular metabolism and sensitivity of tumor energetic
processes to the anticancer drugs.
Key words: mitochondria, respiration, oxidative phosphorylation, NK/Ly,
doxorubicin, landomycin, bafilomicyne, NAADP.