Журнал эволюционной биохимии и физиологии, 2020, T. 56, № 7, стр. 737-737

Mechanism(s) of Modulation of Cd2+-Induced Cytotoxcity by Paxilline and NS1619/NS004: an Involvement of Ca2+-Activated Big-Conductance Potassium Channel and/or Respiratory Chain of Mitochondria?

E. A. Belyaeva 1*, T. V. Sokolova 1

1 Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences
Saint Petersburg, Russia

* E-mail: alenab61@mail.ru

Полный текст (PDF)

The aim of the present study was to investigate molecular mechanisms of modulating action of effectors of Ca2+-activated big-conductance potassium channel (BK(Ca)) against toxicity and cell death evoked by heavy metal ions, cadmium (Cd2+). Experiments were conducted on two cell types (AS-30D, PC12) and isolated liver mitochondria of rat. Previously we observed that cytotoxic effects of Cd2+ decreased in the presence of paxilline - BK(Ca) blocker and enhanced in the presence of NS1619 or NS004 – BK(Ca) openers. In this work we have shown that both BK(Ca) activators under test induce apoptosis of AS-30D cells which is sensitive to paxilline. In the simultaneous presence of Cd2+ and NS1619 or NS004 in the incubation medium the apoptosis of AS-30D cells increased and paxilline had no influence on it. As recently obtained by us, paxilline does not induce apoptosis per se as well as does not affect the Cd2+-induced apoptosis of AS-30D cells. At the same time, paxilline produced transient decrease of maximal, i.e. completely uncoupled, respiration of AS-30D cells, and enlarged the intracellular production of reactive oxygen species, ROS. Besides, paxilline partially inhibited Cd2+-induced necrosis both of AS-30D and PC12 cells. Moreover, paxilline temporally depressed maximal respiration rate of PC12 cells as well and decreased their ROS production in the presence of Cd2+ (Belyaeva, Sokolova, 2020). Using PC12 cells, in the present work we have shown that NS1619 and NS004 do not change significantly the Cd2+-induced ROS generation. Interestingly, maximal decrease of the Cd2+-enhanced ROS formation was observed when PC12 cells were incubated with paxilline in the presence of NS1619 or NS004. The both BK(Ca) openers enhanced harmful effects of Cd2+ on respiration and membrane permeability of isolated rat liver mitochondria in incubation media of different ion content.

Supported by state assignment (АААА-А18-118012290371-3).

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