Book of Abstracts - Australian Centre for Economic Research on ...

23-26 August 2007,
Budapest, Hungary
68
1F_05_P
(poster section A1, poster board #56, 25 th <strong>of</strong> August)
DESIGN OF NOVEL STRESS PROTECTORS BASED ON SHORT
SYNTHETIC PEPTIDES
E. V. Navolotskaya 1 , Y. A. Kovalitskaya 1 , A. A. Kolobov 2 , V. B. Sadovnikov 1
1Branch <strong>of</strong> Shemyakin and Ovchinnikov Institute <strong>of</strong> Bioorganic Chemistry, Pushchino, Moscow Region, Russia;
2State <strong>Research</strong> Center <strong>for</strong> Institute <strong>of</strong> Highly Pure Biopreparations, St. Petersburg, Russia
The work is directed towards the solution <strong>of</strong> one <strong>of</strong> the most important problems <strong>of</strong> modern biology and
medicine – the creation <strong>of</strong> novel effective and safe agents capable <strong>of</strong> elevating adaptation potential <strong>of</strong> the
human body under the influence <strong>of</strong> various extreme factors. The objective <strong>of</strong> the work is synthesis <strong>of</strong> a set <strong>of</strong>
short corticotropin-like peptides and study <strong>of</strong> their effect on non-specific resistance <strong>of</strong> laboratory animals
subjected to various stress factors. It was synthesized 75 <strong>of</strong> corticotropin-like peptides, which contained from
13 to 2 amino acid residues. The ability <strong>of</strong> the synthesized peptides to inhibit the specific binding <strong>of</strong> tritium
labeled corticotropin fragment 11-24 to rat adrenal cortex in vitro was investigated. On the base <strong>of</strong> the
obtained results there were selected 6 peptides (KKRR, KKRRP, VKKPGSSVKV, KKRRLLLL,
LLKKRRLLLL, ac-KKRR-NH 2 ) with the highest inhibitory activity <strong>for</strong> in vivo tests. The influence <strong>of</strong> the
selected peptides on the level <strong>of</strong> glucocorticoids and catecholamines in the adrenals and blood <strong>of</strong> rats in the
experiments on acute hemorrhage and hypobaric hypoxia were studied. It was established that intravenous
injection <strong>of</strong> peptides KKRR, KKRRP or ac-KKRR-NH 2 at the dose <strong>of</strong> 1 µg/kg could correct the changes in
the content <strong>of</strong> corticosterone, adrenaline and noradrenaline in the adrenals and plasma <strong>of</strong> rats that were
subjected to hemorrhagic shock or hypobaric hypoxia. It has been shown that the stress-protective activity <strong>of</strong>
these peptides is mediated by the corticotropin receptor in cortex <strong>of</strong> the adrenals.
1F_06_P
(poster section A1, poster board #57, 25 th <strong>of</strong> August)
PROTECTIVE EFFECT OF A NOVEL MOLECULAR CHAPERONE INDUCER,
PAEONIFLORIN, ON THE HCL-INDUCED GASTRIC MUCOSAL INJURY
Kenzo Ohtsuka, Daisuke Kawashima, Midori Asai
Laboratory <strong>of</strong> Cell & Stress Biology, Department <strong>of</strong> Environmental Biology,
Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan
e-mail: kohtsuka@isc.chubu.ac.jp
Moderate overexpression <strong>of</strong> heat shock proteins (HSPs) or molecular chaperones could confer cells and
tissues stress tolerance and provide beneficial effects on various pathological states associated with protein
misfolding and protein aggregation. Recently, we found a novel chaperone inducing compound, paeoniflorin,
which is one <strong>of</strong> the major constituents <strong>of</strong> a herbal medicine derived from Paeonia lactiflora Pall. Paeoniflorin
could induce Hsp70, Hsp40, and Hsp27 in cultured HeLa cells. Treatment <strong>of</strong> cells with paeoniflorin resulted
in enhanced phosphorylation and acquisition <strong>of</strong> DNA binding ability <strong>of</strong> heat shock factor 1 (HSF1), as well
as the <strong>for</strong>mation <strong>of</strong> characteristic HSF1 granules in the nucleus, suggesting that the induction <strong>of</strong> these HSPs
by paeoniflorin is mediated by the activation <strong>of</strong> HSF1. Also, thermotolerance was induced by the treatment
with paeoniflorin. Paeoniflorin had no apparent toxic effect at concentrations as high as 500 M (Cell Stress
& Chaperones 9: 387-389, 2004).