MiP2005: Session 11

Abstract without presentation                                                Mitochondrial Physiology Network 10.9: 129-130 (2005) - download pdf

 

Increased sensitivity of MPT-pore opening in old rat heart.

VF Sagach, Olena V Rudyk, GL Vavilova, NA Strutyns’ka

Bohomoletz Ins. Physiology, Kiev 01024 Ukraine. - ross@gala.net

    Alterations in the sensitivity of mitochondrial permeability transition pore (MPTP) opening are important for the prevention of aging-induced chronic oxidative stress. Two indices of MPTP opening were used in this study: (i) the swelling-induced decrease in optical density (λ=520 nm) of isolated mitochondria and (ii) the release of a mitochondrial factor (MF, λ=230-260 nm), which is the marker of MPTP-opening.  Some inducers of MPTP-opening CaCl2  (10-7-10-4 M), phenylarsine oxide (PAO, 10-8-10-4 M) and t-butyl-hydroperoxide (t-BuOOH, 10-9-10-3 M) caused more swelling of mitochondria isolated from hearts of old than from adult rats. Mitochondria from old rat hearts  released some MF in the absence of MPTP inducers. The release of MF by CaCl2  (10-7 M) and PAO (10-9 M) was  significantly higher from mitochondria isolated from old than from those from adult rat hearts. Thus mitochondria isolated from old rat hearts possess an increased sensitivity towards CaCl2, PAO and t-BuOOH. It was accompanied by an increase in hydrogen peroxide (23.75±3.93 pmol/ mg protein) and hydroxyl radical  production (3.69±0.81 ΔE*102/30min*mg protein) in old in comparison to adult rat hearts (5.56±0.47 pmol/mg protein and 1.18±0.22 ΔE*102/30min*mg protein, respectively) and by an increase m-RNA of proapoptotic Bax protein. The classical inhibitor of MPTP opening cyclosporin A (10-5 M) inhibited mitochondrial swelling and MF release completely, whereas this inhibitory effect was incomplete in mitochondria from old rat hearts. The antioxidant melatonin (10-5 M) prevented t-BuOOH-induced mitochondrial swelling completely in adult and in old rat heart mitochondria. Thus mitochondria from old hearts are more sensitive to inducers of MPTP opening as a result of aging-induced chronic oxidative stress. These results may be useful for treatment of mitochondrial dysfunction caused by aging.


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