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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2008; 54(4): 3-10


Mitochondrialpermeability transition pore opening inhibition by ecdysterone in heart mitochondriaof aging rats

V.F. Sagach, Yu.P. Korkach, A.V. Kotsuruba, O.V. Rudyk, G.L. Vavilova.

    O.O. Bogomolets Institute of Physiology, NationalAcademy of Sciences of Ukraine, Kyiv;O.V. Palladin Institute of Biochemistry, National Academyof Sciences of Ukraine, Kyiv


Abstract

Nitric oxide reacts rapidly with superoxide to produce the po- tent oxidant peroxynitrite. In vivo mitochondria produce super- oxide as well as NO. In heart mitochondria of aging rats the amount of NO and .O2- are increased thus the levels of peroxynitrite produced may be increased too, in this reason mitochondria may be a major site of peroxynitrite formation. Oxidative stress induces cyclosporine A-sensitive mitochondrial efflux of calcium and proapoptotic factors through MPTP (mi- tochondrial permeability transition pore) opening in heart mito- chondria which may contribute to tissue damage and mitochon- drial dysfunction in aging rats. We tested the levels of NO and superoxide generation in mitochondria simultaneously with cyclosporine A-sensitive MPTP opening by Ca2+ and phenylarsine oxide (PAO) to determine whether down- regulation of both NO and .O2- generation in heart mitochon- dria by potent steroid antioxidant and free radical scavenger ecdysterone may protect heart mitochondria of aging rats again tissue damage. C27-phytosteroid hormone ecdysterone (10mkg/ 100g, per os, 2 weeks) mimics action of its structural analog C27- steroid hormone calcitriol (1?,25- dihydroxyvitamin D3) and exert its cardio protection in aging heart mitochondria by inhibition of MPTP opening with effectivity of action of hormone melatonine (150mkg/100g, 2 weeks [ V.F.Sagach et al. Fyziol. J (Ukr), 2006, 52(2), 3-15]). MPTP inhibition is dependent on paradoxycally high activation by ecdusterone of oxidative deg- radation of L- arginine by mtcNOS in mitochondria, by down- regulation of superoxide generation and L-arginine degradation by arginase II and NO generation by mtiNOS in de novo and by NADP-dependent mtNR (nitrate reductase) in salvage path- ways . These results suggest that MPTP opening may be di- rectly influenced by ecdysterone signaling in mitochondria. The signaling pathway by which ecdysterone may coregulate the .O2- and NO generation in heart mitochondria of aging rats may involve an outer mitochondrial membrane estrogen receptor coupled to mitochondrial PI3K/Akt/PKB activation results in superactivation and constitutive NO synthesis by mtcNOS .

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© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.