Role of Mitochondrial Respiratory Chain in Neurotoxic Action of Heavy Metals: Comparison of Cd2+, Hg2+ and Cu2+
The aim of the work search out elucidate the duty of mitochondrial energized matter transport chain (mtETC) in neurotoxicity of burdensome metals, to a degree Cd2+, Hg2+ and Cu2+. In particular, the effects of these bivalent sounds that are pleasant ions on container being, intracellular sensitive oxygen species creation, breathing and mitochondrial sheath potential of informer neuron-like PC12 cell line were intentional in the deficiency and in the occupancy of miscellaneous antioxidants and mitochondrial function modulators. As revealed, the metals substitute precipitated, even though in a different way, prescription- and opportunity-helpless changes of all earlier parameters. Noteworthy, origin from 10 µM and before at short process of early development period (3 h), Cd2+ significantly shy rates of maximally uncoupled container breathing. In addition, nearly complete suppression of basic breathing was worked out later 3 h of incubation accompanying 50 µM Hg2+ or 500 µM Cd2+, inasmuch as even later 48 h of exposure to 500 µM Cu2+, only 50% abolition of breathing accepted place. It has happened established that not only miscellaneous antioxidants (N-acetylcysteine, butylhydroxytoluene, mannitol, source of nourishment E, tetramethylpiperidine-1-oxyl) and inhibitors of mitochondrial permeability change (MPT) pores (cyclosporin A, bongkrekic acid, ruthenium maroon), but also specific mtETC modulators as FCCP (a established pretended uncoupler) and stigmatellin (a complex III prevention), partially preserve from container damage caused by Cd2+. However, all secondhand mtETC modulators did not save against Hg2+- or Cu2+-persuaded container injury. Importantly, stigmatellin was proved expected individual of the most forceful protectors against Cd2+-persuaded container damage, bearing a 15-20% increase in container viability. Molecular systems of the engrossment of mtETC in form of rock and roll-inferred mitochondrial membrane permeabilization and container obliteration are reviewed. As a result, the connection between mtETC and MPT pore has enhance more apparent.
Elena A. Belyaeva,
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Thorez pr. 44, 194223, St.-Petersburg, Russia.
Please see the link here: https://stm.bookpi.org/CERB-V2/article/view/8893
Keywords: Cadmium, mercury, copper, cytotoxicity mechanism(s), mitochondrial electron transport chain, mitochondrial permeability transition pore, stigmatellin