Retinal progenitor cells （RPCs） are neural stem cells able to differentiate into any normal adult retinal cell type, except for pigment epithelial cells. Retinoic acid （RA） is a powerful growth/differentiation fac...Retinal progenitor cells （RPCs） are neural stem cells able to differentiate into any normal adult retinal cell type, except for pigment epithelial cells. Retinoic acid （RA） is a powerful growth/differentiation factor that generally causes growth inhibition, differentiation and/or apoptosis. In this study, we demonstrate that RA not only affects mouse RPC differentiation but also improves cell survival by reducing spontaneous apoptotic rate without affecting RPC proliferation. The enhanced cell survival was accompanied by a significant upregulation of the expression of protein kinase A （PKA） and several protein kinase C （PKC） isoforms. Treatment of cells grown in RA-free media with 8-bromoadenosine3＇,5＇-cyclic monophosphate, a known activator of PKA, resulted in an anti-apoptotic effect similar to that caused by RA; whereas the PKA inhibitor N-[2-（p-bromocinnamylamino）ethyl]-5-isoquinolinesul- fonamide dihydrochloride led to a significant （-32%） increase in apoptosis. In contrast, treatment of RPCs with any of two PKC selective inhibitors, 2,2＇,3,3＇,4,4＇-hexahydroxy-1,1 ＇-biphenyl-6,6＇-dimethanol dimethyl ether and bisindolylmaleimide XI, led to diminished apoptosis; while a PKC activator, phorbol 12-myristate 13-acetate, increased apoptosis. These and other data suggest that the effect of RA on RPC survival is mostly due to the increased anti-apoptotic activity elicited by PKA, which might in turn be antagonized by PKC. Such a mechanism is a new example of tight regulation of important biological processes triggered by RA. Although the detailed mechanisms remain to be elucidated, we provide evidence that the pro-survival effect of RA on RPCs is not mediated by changed expression of p53 or bcl-2, and appears to be independent of 15-amyloid, Fas ligand, TNF-α, ganglioside GM1 and ceramide C 16-induced apoptotic pathways.展开更多
A scorpion-shaped di-NBD(4-substituted-7-nitrobenzoxadiazole) derivative of cholesterol(Chol-2NBD) was designed and synthesized. The gelation behaviors of the compound in a series of single and mixed liquids were test...A scorpion-shaped di-NBD(4-substituted-7-nitrobenzoxadiazole) derivative of cholesterol(Chol-2NBD) was designed and synthesized. The gelation behaviors of the compound in a series of single and mixed liquids were tested. It was shown that the compound is an effective gelator for mixture liquids of THF and benzene at room temperature. Furthermore, FT-IR and temperature-/concentration-dependent 1H NMR spectroscopy studies revealed that hydrogen bonding and π-π stacking among the molecules of Chol-2NBD are two main driving forces for the physical gelation of the mixture liquids. Interestingly, as observed in the gelation test and confirmed by rheological studies, the Chol-2NBD-THF/benzene gel systems, at least the one with 2:8 of the volume ratio of THF to benzene, are mechanically stable, but very sensitive to the stimulus of shear stress, which means that the gel changes into a liquid upon shaking. More interestingly, the liquid returns to gel instantly once the shear stress is removed. This phase transition process could be repeated for many times at room temperature. In addition, primary tests demonstrated that the fluorescence emission of Chol-2NBD is significantly quenched by the presence of water, ammonia water, or ammonia gas, but the emission recovers after evaporation of them. Further detailed investigation is under progress.展开更多
文摘Retinal progenitor cells （RPCs） are neural stem cells able to differentiate into any normal adult retinal cell type, except for pigment epithelial cells. Retinoic acid （RA） is a powerful growth/differentiation factor that generally causes growth inhibition, differentiation and/or apoptosis. In this study, we demonstrate that RA not only affects mouse RPC differentiation but also improves cell survival by reducing spontaneous apoptotic rate without affecting RPC proliferation. The enhanced cell survival was accompanied by a significant upregulation of the expression of protein kinase A （PKA） and several protein kinase C （PKC） isoforms. Treatment of cells grown in RA-free media with 8-bromoadenosine3＇,5＇-cyclic monophosphate, a known activator of PKA, resulted in an anti-apoptotic effect similar to that caused by RA; whereas the PKA inhibitor N-[2-（p-bromocinnamylamino）ethyl]-5-isoquinolinesul- fonamide dihydrochloride led to a significant （-32%） increase in apoptosis. In contrast, treatment of RPCs with any of two PKC selective inhibitors, 2,2＇,3,3＇,4,4＇-hexahydroxy-1,1 ＇-biphenyl-6,6＇-dimethanol dimethyl ether and bisindolylmaleimide XI, led to diminished apoptosis; while a PKC activator, phorbol 12-myristate 13-acetate, increased apoptosis. These and other data suggest that the effect of RA on RPC survival is mostly due to the increased anti-apoptotic activity elicited by PKA, which might in turn be antagonized by PKC. Such a mechanism is a new example of tight regulation of important biological processes triggered by RA. Although the detailed mechanisms remain to be elucidated, we provide evidence that the pro-survival effect of RA on RPCs is not mediated by changed expression of p53 or bcl-2, and appears to be independent of 15-amyloid, Fas ligand, TNF-α, ganglioside GM1 and ceramide C 16-induced apoptotic pathways.
基金supported by the National Natural Science Foundation of China(91027017 and 21273141)the Ministry of Education of China for its"Program for Changjiang Scholars and Innovative Research Team in University"of China(IRT1070)
文摘A scorpion-shaped di-NBD(4-substituted-7-nitrobenzoxadiazole) derivative of cholesterol(Chol-2NBD) was designed and synthesized. The gelation behaviors of the compound in a series of single and mixed liquids were tested. It was shown that the compound is an effective gelator for mixture liquids of THF and benzene at room temperature. Furthermore, FT-IR and temperature-/concentration-dependent 1H NMR spectroscopy studies revealed that hydrogen bonding and π-π stacking among the molecules of Chol-2NBD are two main driving forces for the physical gelation of the mixture liquids. Interestingly, as observed in the gelation test and confirmed by rheological studies, the Chol-2NBD-THF/benzene gel systems, at least the one with 2:8 of the volume ratio of THF to benzene, are mechanically stable, but very sensitive to the stimulus of shear stress, which means that the gel changes into a liquid upon shaking. More interestingly, the liquid returns to gel instantly once the shear stress is removed. This phase transition process could be repeated for many times at room temperature. In addition, primary tests demonstrated that the fluorescence emission of Chol-2NBD is significantly quenched by the presence of water, ammonia water, or ammonia gas, but the emission recovers after evaporation of them. Further detailed investigation is under progress.
