[Novel compounds increasing chaperone Hsp70 expression and their biological activity].
Hsp70 possesses chaperonic activity, the property associated with the protective function that was demonstrated in experiments on a great number of cell and animal models. Therefore, it seems important to search for the substances able to innocuously elevate the chaperone concentration in an organism cells and tissues. In our work, we screened of more that 60 compounds and found two chemicals, derivatives of shikonin and echinochrome that able to increase the chaperone level in a variety of human cells. It was shown that in human erythroleukemia K562 cells treated with the both substances concomitantly with elevation of Hsp70 level the absolute chaperonic activity was also increased; this can indicate mobilization of the whole cellular chaperonic machinery by above mentioned compounds. Estimating biological activity of the two substances, we demonstrated that treatments of cells by them prior to hard heat stress, hydrogen peroxide or staurosporine reduced cell mortality by 20-50 % depending on a cytotoxic factor. The results show that after simple chemical modifications these compounds might be taken as a basis of pharmaceuticals for therapy of wide range of disorders.
Eremenko
E M
EM
Antimonova
O I
OI
Shekalova
O G
OG
Polonik
S G
SG
Margulis
B A
BA
Guzhova
I V
IV
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D020014:K562 Cells; D029684:Lithospermum / Q000737:chemistry; D009285:Naphthoquinones / Q000737:chemistry* / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012617:Sea Urchins / Q000737:chemistry
D004365:Drugs, Chinese Herbal; D018840:HSP70 Heat-Shock Proteins; D009285:Naphthoquinones; C007573:echinochrome A