Chen Y, Derguini F, Buck J
Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10205-8. doi: 10.1073/pnas.94.19.10205.
Murine 3T3 cells arrest in a quiescent, nondividing state when transferred into medium containing little or no serum. Within the first day after transfer, fibroblasts can be activated to proliferate by platelet-derived growth factor (PDGF) alone; cells starved longer than 1 day, however, are activated only by serum. We demonstrate that endogenous vitamin A (retinol) or retinol supplied by serum prevents cell death and that retinol, in combination with PDGF, can fully replace serum in activating cells starved longer than 1 day. The physiological retinol derivative 14-hydroxy-4, 14-retro-retinol, but not retinoic acid, can replace retinol in rescuing or activating 3T3 cells. Anhydroretinol, another physiological retinol metabolite that acts as a competitive antagonist of retinol, blocks cell activation by serum, indicating that retinol is a necessary component of serum. It previously has been proposed that activation of 3T3 cells requires two factors in serum, an activation factor shown to be PDGF and an unidentified survival factor. We report that retinol is the survival factor in serum.
当转移到含有很少或不含血清的培养基中时,小鼠3T3细胞会停滞在静止、非分裂状态。在转移后的第一天内,成纤维细胞仅通过血小板衍生生长因子(PDGF)就可被激活而增殖;然而,饥饿超过1天的细胞仅在血清作用下才被激活。我们证明内源性维生素A(视黄醇)或血清提供的视黄醇可防止细胞死亡,并且视黄醇与PDGF联合使用时,在激活饥饿超过1天的细胞方面可完全替代血清。生理性视黄醇衍生物14-羟基-4,14-反式视黄醇而非视黄酸,可替代视黄醇来挽救或激活3T3细胞。脱水视黄醇是另一种作为视黄醇竞争性拮抗剂的生理性视黄醇代谢产物,它可阻断血清对细胞的激活作用,这表明视黄醇是血清的必要成分。此前有人提出,3T3细胞的激活需要血清中的两种因子,一种已被证明是PDGF的激活因子和一种未知的存活因子。我们报告视黄醇就是血清中的存活因子。