Thiolutin (N-(4-methyl-5-oxodithiolo[4,3-b]pyrrol-6-yl)acetamid)
a aureothricin (N-(4-methyl-5-oxodithiolo[4,3-b]pyrrol-6-yl)propanamid) jsou síru-obsahující
širokospektrá antibiotika produkovaná některými kmeny streptomycet (Nishimura a
Kimura 1953; Maeda 1953; Celmer a Solomion 1955). Aurethricin je vyšším
homologem thiolutinu (Martin et al. 1963) a byl izolován Umezavou et al. (1946)
jako antibiotikum streptomycet. Jejich biosyntéza byla studována Sturdíkovou et
al. (1990).
Thiolutin blokuje elongaci mRNA tím, že inhibuje RNA polymerázy I, II i III (Jimenez et al. 1973; Khachatourians a Tipper 1974; Pelechano a Pérez-Ortín 2008). Inhibuje také tvorbu glukanu a mannanu u kvasinek (Tipper 1973) a narušuje tak tvorbu jejich buněčné membrány (Elorza et al. 1976). Studie též prokázaly, že thiolutin inhibuje adhezi HUVEC buněk (human umbilical vein endothelial cells) na vitronectin, čímž potlačuje angiogenézu vyvolanou rakovinnou buňkou (Minamiguchi et al. 2001). Thiolutin je silným induktorem fosforylace Hsp27 (heat shock protein) (Dai et al. 2008). Protein Hsp27 je asociován s komponentami intermediálních filament, vimentinem a nestinem. Thiolutin ruší interakci Hsp27 s nestinem. To ukazuje na nový mechanismus regulace buněčné adheze a na dynamiku cytoskeletu Hsp27 (Jia et al. 2010).
Literatura Celmer WD, Solomon IA. The structures of thiolutin and aureothrici, antibiotics containing a unique pyrrolinodithiol nucleus. J Am Chem Soc 1955; 77: 2861-2865. Dai S, Jia Y, Wu SL, Isenberg JS, Ridnour LA, Bandle RW, Wink DA, Roberts DD, Karger BL. Comprehensive characterization of heat shock protein 27 phosphorylation in human endothelial cells stimulated by the microbial dithiole thiolutin. Proteome Res. 2008; 7: 4384-4395. Elorza MV, Lostau CM, Villanueva JR, Sentandreu R. Cell wall synthesis regulation in Saccharomyces cerevisiae. Effect of RNA and protein inhibition. Biochim Biophys Acta. 1976; 454: 263-272. Jia Y, Wu SL, Isenberg JS, Dai S, Sipes JM, Field L, Zeng B, Bandle RW, Ridnour LA, Wink DA, Ramchandran R, Karger BL, Roberts DD. Thiolutin inhibits endothelial cell adhesion by perturbing Hsp27 interactions with components of the actin and intermediate filament cytoskeleton. Cell Stress Chaperones. 2010; 15: 165-181. Jimenez A, Tipper DJ, Davies J. Mode of action of thiolutin, an inhibitor of macromolecular synthesis in Saccharomyces cerevisiae. Antimicrob Agents Chemother. 1973; 3: 729-738. Khachatourians GG, Tipper DJ. Inhibition of messenger ribonucleic acid synthesis in Escherichia coli by thiolutin. J Bacteriol. 1974; 119:795-804. Maeda K. Chemical studies on antibiotic substances. IV. A crystalline toxic substance of Streptomyces thioluteus producing aureothricin. J Antibiot (Tokyo). 1953; 6: 137-138. Martin JH, Groth WC, Hausmann WK. Identification by X-ray powder diffraction of thiolutin and aureothricin isolated by paper chromatography. Antimicrob Agents Chemother (Bethesda). 1963; 15: 130-133. Minamiguchi K, Kumagai H, Masuda T, Kawada M, Ishizuka M, Takeuchi T. Thiolutin, an inhibitor of HUVEC adhesion to vitronectin, reduces paxillin in HUVECs and suppresses tumor cell-induced angiogenesis. Int J Cancer. 2001; 93: 307-316. Nishimura H, Kimura T. On a yellow crystalline antibiotic, identical with aureothricin isolated from a new species of streptomyces, 39a, and its taxonomic study. J Antibiot (Tokyo). 1953; 6: 57-65. Pelechano V, Pérez-Ortín JE. The transcriptional inhibitor thiolutin blocks mRNA degradation in yeast. Yeast. 2008; 25: 85-92. Sturdíková M, Proksa B, Uhrín D, Fuska J. Regulation of biosynthesis of thiolutin and aureothricin in Streptomyces kasugaensis. Folia Microbiol (Praha). 1990; 35: 278-283. Tipper DJ. Inhibition of yeast ribonucleic acid polymerases by thiolutin. J Bacteriol. 1973; 116: 245-256. Umezawa H, Maeda K, Kosaka A. Isolation of a new antibiotic substance, aureothricin from a strain of Streptomyces. Jpn. Med. J. 1949; 1: 512-517.
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