Melanin counter act puromycin-induced inhibition of collagen and DNA biosynthesis in human skin fibroblasts.

摘要: Abstract Puromycin is an experimental anti-tumor antibiotic acting through inhibition of protein synthesis. Because its untoward side effects (as inner ear and renal lesions) the was not approved for clinical trials. The mechanism underlying organ specificity effect understood. In view fact that a number drugs form with melanin complexes affect their pharmacological activity, we determined whether puromycin interacts how this process affects biosynthesis collagen in cultured human skin fibroblasts. Our results indicate forms melanin. amount bound to increases increase initial drug concentration. Scatchard plot analysis binding has shown at least two classes independent sites are implicated puromycin-melanin complex formation: one class strong association constant K 1 = 1.84 × 10 6 M −1 , second weak 2 5.26 3 . total were n 0.1260 0.2861 μmol per mg We found induced DNA (IC 50 ∼ μM). Melanin 100 μg/ml produced about 20% synthesis, but it had no on However, addition (100 μg/ml) - treated cells (2 μM) abolished inhibitory action biosynthesis. have suggested IGF-I receptor expression, involved metabolism, may be targets It decrease expression as well MAP kinases expression: ERK1 ERK2 by Western immunoblot analysis. These data suggest tissue specific activity depend abundance tissues.