.ALPHA.-Tocopheryl Succinate Activates Protein Kinase C in Cellular and Cell-Free Systems

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

“…4) [ 43]. The existence probability of the superimposed conformation of TECS was approximately 1/1,000, indicating that 1/1,000 of the TS molecules surrounding PKC would bind to the phorbol ester-binding domain [43]. The high structural flexibility of TS demonstrated by the theoretical computation suggests that the interaction of TS with various signal transduction protein such as PKC produces its versatile effects.…”

“…Similarly, Bang et al reported that TS treatment induced a gradual increase in PKC activity in HL-60 cells [ 42 ]. In addition, TS induced auto-phosphorylation of PKC ␣ in rat VSMC [ 43 ]. From these results, PKC is thought to be the key kinase in the process of the TS effects.…”

“…TS increased the activity of isolated PKC in a cellfree system like phorbol ester phorbol 12-myristate 13-acetate (PMA), although the effective concentra- tions of TS were significantly higher than those of PMA [ 43 ]. On the contrary, Gopalakrishna et al…”

“…We further found that the 156th conformer from the most stable conformation of TECS superimposed on the active conformer of PMA model compound 4 ␤ -OH-phorbol 12 ␤ , 13 ␣ -diacetate ( ␤ PAA) (Fig. 4) [ 43]. The existence probability of the superimposed conformation of TECS was approximately 1/1,000, indicating that 1/1,000 of the TS molecules surrounding PKC would bind to the phorbol ester-binding domain [43].…”

“…These results suggest that TS interacts directly with PKC. From the computational approach using a model compound of TS 2,5,7,8-tetramethyl-2-ethyl-chroman-6-yl succinate (TECS), we showed that the structure of the succinyl moiety is highly flexible [ 43 ]. We further found that the 156th conformer from the most stable conformation of TECS superimposed on the active conformer of PMA model compound 4 ␤ -OH-phorbol 12 ␤ , 13 ␣ -diacetate ( ␤ PAA) (Fig.…”