On Friday, February 12, 2010 at 1:40:37 PM UTC+9, Olafur Pall Olafsson wrote:
This study has been posted on this group before but I just happened to
came across it and just finished reading the full text. I am posting
it below along with quotes from the full text article.
Biochemistry (Mosc). 2007 Dec;72(12):1385-96.
A biochemical approach to the problem of aging: "megaproject" on membrane-penetrating ions. The first results and prospects.
Skulachev VP.
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119991, Russia. skulach@belozersky.msu.ru
Antioxidants specifically addressed to mitochondria have been studied
for their ability to decelerate aging of organisms. For this purpose,
a project has been established with participation of several research
groups from Belozersky Institute of Physico-Chemical Biology and some
other Russian research institutes as well as two groups from the USA
and Sweden, with support by the "Mitotechnology" company founded by
"RAInKo" company (O. V. Deripaska and Moscow State University). This
paper summarizes the first results of the project and estimates its prospects. Within the framework of the project, antioxidants of a new
type (SkQ) were synthesized comprising plastoquinone (an antioxidant
moiety), a penetrating cation, and decane or pentane linker. Using
planar bilayer phospholipid membranes, we selected SkQ derivatives
with the highest penetrating ability, namely plastoquinonyl-decyl- triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19
(SkQR1), and methylplastoquinonyl-decyl-triphenylphosphonium (SkQ3).
Anti- and prooxidant properties of these substances and also of
ubiquinone and ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were
tested on isolated mitochondria. Micromolar concentrations of cationic quinones are found to be very strong prooxidants, but in lower (sub- micromolar) concentrations they display antioxidant activity. The
antioxidant activity decreases in the series SkQ1=SkQR1>SkQ3>MitoQ, so
the window between the anti- and prooxidant effects is smallest for
MitoQ. SkQ1 is rapidly reduced by complexes I and II of the
mitochondrial respiratory chain, i.e. it is a rechargeable
antioxidant. Extremely low concentrations of SkQ1 and SkQR1 completely
arrest the H2O2-induced apoptosis in human fibroblasts and HeLa cells
(for SkQ1 C1/2=1.10(-9) M). Higher concentrations of SkQ are required
to block necrosis initiated by reactive oxygen species (ROS). In mice,
SkQ1 decelerates the development of three types of accelerated aging (progeria) and also of normal aging, and this effect is especially demonstrative at early stages of aging. The same pattern is shown in invertebrates (drosophila and daphnia). In mammals, the effect of SkQs
on aging is accompanied by inhibition of development of such age-
related diseases as osteoporosis, involution of thymus, cataract, retinopathy, etc. SkQ1 manifests a strong therapeutic action on some
already developed retinopathies, in particular, congenital retinal
dysplasia. With drops containing 250 nM SkQ1, vision is recovered in
50 of 66 animals who became blind because of retinopathy. SkQ1-
containing drops instilled in the early stage of the disease prevent
the loss of sight in rabbits with experimental uveitis and restore
vision to animals that had already become blind. A favorable effect is
also achieved in experimental glaucoma in rabbits. Moreover, the
pretreatment of rats with 0.2 nmol SkQ1 per kg body weight
significantly decreases the H2O2-induced arrhythmia of the isolated
heart. SkQ1 strongly reduces the damaged area in myocardial infarction
or stroke and prevents the death of animals from kidney infarction. In
p53-/- mice, SkQ1 decreases the ROS level in the spleen cells and
inhibits appearance of lymphomas which are the main cause of death of
such animals. Thus, it seems reasonable to perform clinical testing of
SkQ preparations as promising drugs for treatment of age-related and
some other severe diseases of human and animals.
PMID: 18205623 [PubMed - indexed for MEDLINE]
# An attempt to prevent senescence: a mitochondrial approach.
Biochim Biophys Acta. 2009 May; 1787(5):437-61. Epub 2008 Dec 29.
[Biochim Biophys Acta. 2009]
# Mitochondria-targeted plastoquinone derivatives as tools to
interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies.
Biochemistry (Mosc). 2008 Dec; 73(12):1273-87.
[Biochemistry (Mosc). 2008]
# Mitochondria-targeted plastoquinone derivatives as tools to
interrupt execution of the aging program. 2. Treatment of some ROS-
and age-related diseases (heart arrhythmia, heart infarctions, kidney ischemia, and stroke).
Biochemistry (Mosc). 2008 Dec; 73(12):1288-99.
[Biochemistry (Mosc). 2008]
# Mitochondria-targeted plastoquinone derivatives as tools to
interrupt execution of the aging program. 4. Age-related eye disease.
SkQ1 returns vision to blind animals.
Biochemistry (Mosc). 2008 Dec; 73(12):1317-28.
[Biochemistry (Mosc). 2008]
# ReviewHow to clean the dirtiest place in the cell: cationic
antioxidants as intramitochondrial ROS scavengers.
IUBMB Life. 2005 Apr-May; 57(4-5):305-10.
Quotes from the full text:
"The effect of SkQ1 was studied on aging of normal mice without any
form of progeria. SkQ1 (0.5, 5, or 50 nmol/kg) noticeably decreased
the age related mortality of the animals, and the effect was
especially demonstrative on the first 20% of the deceased animals
(Fig. 4). The lifespan of these animals was increased 2.5 fold. For
50% of the deceased animals the effect was 30%, and for the long lived
mice (the last 20% of the cohort studied) it was only 15%. In other
words, the so called rectangularization of the mortality curve took
place. Similar effect was revealed for invertebrates—Drosophila (data
of E. G. Pasyukova et al., Institute of molecular Genetics) and
Daphnia (data of O. F. Filenko, Faculty of Biology, Moscow State University)."
"Our data on the effect of SkQ1 and SkQR1 on animals in vivo are
summarized in Table 2. One can see that 20 different signs of aging
are mitigated by SkQs, a fact suggesting that SkQs are potent
geroprotectors. It is remarkable that the geroprotective effect of
SkQ1 consists
not only in an increase in the lifespan but also in improvement of the quality of life during the second half of the life. In other words, it prolongs youth."
Hey Olaf, is this Sk/MitoQ also protecting cancer cells from oxidative stress and apoptosis? The oxidative stress is sometimes needed, e.g. the immune system uses chlorine dioxide to kill cells that went awry and invaders ...
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