Respondent

Hreniukh Volodymyr Petrovych

Theme

Peculiarities  of  bioenergetic  processes  in  mitochondria  of Nemeth-Kelner lymphoma cells.

Defence Date

08.04.2016

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.

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