Jongwook Park

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

Aims/hypothesisNeurodegenerative changes in the diabetic retina occurring before diabetic retinopathy could be inevitable by the altered energy (glucose) metabolism, in the sense that dynamic image-processing activity of the retinal neurons is exclusively dependent on glucose. We therefore investigated the morphological changes in the neural retina, including neuronal cell death, of a streptozotocin-induced model of diabetes.MethodsStreptozotocin was intravenously injected. Rats were maintained hyperglycaemic without insulin treatment for 1 week and 4, 8, 12, and 24 weeks, respectively. Diabetic retinas were processed for histology, electron microscopy, and immunohistochemistry using the TUNEL method.ResultsA slight reduction in the thickness of the inner retina was observed throughout the diabetic retinas and a remarkable reduction was seen in the outer nuclear layer 24 weeks after the onset of diabetes. The post-synaptic processes of horizontal cells in the deep invaginations of the photoreceptors showed degeneration changes from 1 week onwards. A few necrotic ganglion cells were observed after 4 weeks. At 12 weeks, some amacrine cells and a few horizontal cells showed necrotic features. Three to seven cellular layers in the outer nuclear layer and nerve terminals, rolled by the fine processes of the Müller cells near the somata of the degenerated ganglion cells, were apparent at 24 weeks. Apoptosis appeared in a few photoreceptor cells at 4 weeks, and the number of apoptotic photoreceptors increased thereafter.Conclusion/interpretationThese findings suggest that the visual loss associated with diabetic retinopathy could be attributed to an early phase of substantial photoreceptor loss, in addition to later microangiopathy.

Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction

Proteolytic degradation of the extracellular matrix and tumor metastasis correlate with the expression of endopeptidases known as matrix metalloproteinases (MMPs). The expression of MMPs is regulated by cytokines and signal transduction pathways, including those activated by phorbol myristate acetate (PMA). We found that resveratrol, a phytoalexin present in grapes, significantly inhibits the PMA-induced increase in MMP-9 expression and activity. These effects of resveratrol are dose dependent and correlate with the suppression of MMP-9 mRNA expression levels. PMA caused about a 23-fold increase in MMP-9 promoter activity, which was suppressed by resveratrol. Transient transfection utilizing MMP-9 constructs, in which specific transcriptional factors were mutagenized, indicated that the effects of PMA and resveratrol were mediated via an activator protein-1 and nuclear factor-κB response element. Resveratrol inhibited PMA-mediated activation of c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)-δ activation. Therefore, we conclude that the MMP-9 inhibition activity of resveratrol and its inhibition of JNK and PKC-δ may have a therapeutic potential, given that a novel means of controlling growth and invasiveness of tumors.

Exceedingly efficient deep-blue electroluminescence from new anthracenes obtained using rational molecular design

9,10-Bis(3′,5′-diphenylphenyl)anthracene [MAM], 9-(3′,5′-diphenylphenyl)-10-(3‴,5‴-diphenylbiphenyl-4″-yl)anthracene [MAT], and 9,10-bis(3″,5″-diphenylbiphenyl-4′-yl)anthracene [TAT] were newly synthesized through boration and Suzuki aryl–aryl coupling reactions. We have demonstrated that the EL performance of blue-light emitters can be optimized and improved by varying the chemical structures of the side groups. In the thin film state, the three materials exhibit PLmax values in the range of 439–445 nm. MAM, MAT, and TAT all have high Tg values above 120 °C; TAT has the highest Tg value, above 150 °C. This is twice as high as that of DPVBi (64 °C) and is much higher than that of MADN (120 °C) as well. It also exhibits excellent color coordinates (0.156, 0.088), which are very close to the NTSC blue standard, and an external quantum efficiency of 7.18%, twice that of MADN, which are the best reported results for deep-blue OLED emitters.

New deep-blue emitting materials based on fully substituted ethylene derivatives

New blue fluorescent compounds containing tetra-substituted ethylene moieties have been designed and synthesized. These materials, 1,2-di(4′-tert-butylphenyl)-1,2-bis(4′-(anthracene-9-yl)phenyl)ethene [BPBAPE, 1A], 1,2-diphenyl-1,2-bis(4′-(anthracene-9-yl)phenyl)ethene [PBAPE, 1B], 9,10-bis(4-(1,2,2-tris(4-tert-butylphenyl)vinyl)phenyl)anthracene [BTBPPA, 2A], and 9,10-bis(4-(1,2,2-triphenylvinyl)phenyl)anthracene [BTPPA, 2B], were synthesized through Suzuki and McMurry reactions. By fabricating multilayered non-doped OLED devices using these new blue materials, we achieved luminance efficiencies of 4.00 lm W−1 (10.33 cd A−1 at 8.1 V) for BPBAPE [1A] and 1.82 lm W−1 (3.93 cd A−1 at 6.8 V) for BTPPA [2B] at 10 mA cm−2. The maxima in the electroluminescence spectra of ITO/2-TNATA (60 nm)/NPB (15 nm)/BPBAPE [1A] and BTPPA [2B] (30 nm)/Alq3 (30 nm)/LiF (1 nm)/Al (200 nm) devices were found to be 475 and 452 nm respectively. The BPBAPE [1A] and BTPPA [2B] devices exhibited sky blue emission (0.195, 0.303) and deep blue emission (0.159, 0.135) at 10 mA cm−2 respectively.

Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells

Evodiamine is one of the major bioactive compounds that have been isolated and purified from the fruit of Evodiae fructus. Evodiamine exhibits antitumor activities against the human tumor cells, including multidrug-resistant tumor cells. However, the molecular mechanism involved in cell death induced by evodiamine treatment remains poorly understood. In the present study, we showed that evodiamine activated the caspase-dependent apoptotic pathway. This apoptosis was only partially inhibited by a pancaspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, which suggested that evodiamine-induced apoptosis in leukemic U937 cells is partially caspase independent. We observed the nuclear translocation of apoptosis-inducing factor in evodiamine-induced apoptosis of U937 cells, which may be responsible for the caspase-independent apoptotic execution. We next showed that evodiamine induced the substantial amount of apoptosis both in Bcl-2- and Akt-overexpressing U937 cells but not in human peripheral blood mononuclear cells. Although benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone inhibited caspase activity in Bcl-2-overexpressing U937 cells, it completely prevented neither the induction of apoptosis or the nuclear translocation of apoptosis-inducing factor, which suggests that evodiamine is, at least in part, able to bypass the resistance of leukemia cells via caspase-independent apoptotic pathways. Thus, therapeutic strategy using evodiamine may warrant further evaluation. [Mol Cancer Ther 2006;5(9):2398–409]

Synthesis and electroluminescence properties of highly efficient blue fluorescence emitters using dual core chromophores

We describe two novel blue emission materials based on a new type of dual core concept. 1-Phenyl-6-(10-phenyl-anthracen-9-yl)-pyrene (Ph-AP-Ph) and 1-[1,1′;3′,1′′]terphenyl-5′-yl-6-(10-[1,1′;3′,1′′]terphenyl-5′-yl-anthracen-9-yl)-pyrene (TP-AP-TP) were synthesized through boronylation and Suzuki coupling reactions. The Tg values of Ph-AP-Ph and TP-AP-TP were 228 °C and 243 °C, respectively, compared to values of 135 °C and 139 °C for the single core materials 9-(3′,5′-diphenylphenyl)-10-(3′′′,5′′′-diphenylbiphenyl-4′′-yl)anthracene (MAM) and 1,6-bis-[1,1′;3′,1′′]terphenyl-5′-yl-pyrene (TP-P-TP). One of the dual core derivatives, TP-AP-TP, exhibited an ELmax value of 456 nm and a high luminance EQE of 7.51% when used in an EL device. The dual core chromophore materials had narrower PL and EL spectra and better thermal properties than the single core chromophore materials. A device based on TP-AP-TP showed twice the lifetime of a device based on the commercialized material, 2-methyl-9,10-bis(naphthalen-2-yl)anthracene (MADN).

Dual efficiency enhancement by delayed fluorescence and dipole orientation in high-efficiency fluorescent organic light-emitting diodes

To explain the origin of extremely high efficiencies of deep-blue fluorescent organic light-emitting diodes(OLEDs) with anisotropic-shapedanthracene derivatives, the enhancements of singlet-exciton generation efficiency and outcoupling efficiency were investigated by transient electroluminescence measurement and variable angle spectroscopic ellipsometry, respectively. Both the delayed fluorescence from singlet excitons generated via triplet-triplet annihilation and the outcoupling enhancement by dipole orientation of emitters were found to contribute to the high external quantum efficiencies of the devices. This dual efficiency enhancement is important for understanding and further improving high-performance fluorescent OLEDs.

The Origin of the Improved Efficiency and Stability of Triphenylamine-Substituted Anthracene Derivatives for OLEDs: A Theoretical Investigation†

Herein, we describe the molecular electronic structure, optical, and charge-transport properties of anthracene derivatives computationally using density functional theory to understand the factors responsible for the improved efficiency and stability of organic light-emitting diodes (OLEDs) with triphenylamine (TPA)-substituted anthracene derivatives. The high performance of OLEDs with TPA-substituted anthracene is revealed to derive from three original features in comparison with aryl-substituted anthracene derivatives: 1) the HOMO and LUMO are localized separately on TPA and anthracene moieties, respectively, which leads to better stability of the OLEDs due to the more stable cation of TPA under a hole majority-carrier environment; 2) the more balanceable hole and electron transport together with the easier hole injection leads to a larger rate of hole-electron recombination, which corresponds to the higher electroluminescence efficiency; and 3) the increasing reorganization energy for both hole and electron transport and the higher HOMO energy level provide a stable potential well for hole trapping, and then trapped holes induce a built-in electric field to prompt the balance of charge-carrier injection.

Rottlerin induces apoptosis via death receptor 5 (DR5) upregulation through CHOP-dependent and PKC δ-independent mechanism in human malignant tumor cells

Rottlerin has been shown to induce antiproliferation and apoptosis of human cancer cell lines. In this study, we demonstrate a novel mechanism of rottlerin-induced apoptosis via death receptor (DR) 5 upregulation. We found that treatment with rottlerin significantly induces DR5 expression both at its messenger RNA and protein levels. Downregulation of DR5 expression with small-interfering RNA (siRNA) efficiently attenuated rottlerin-induced apoptosis, showing that the critical role of DR5 in this cell death. Rottlerin-induced DR5 upregulation was accompanied by CCAAT/enhancer-binding protein-homologous protein (CHOP) protein expression and rottlerin-induced increase of DR5 promoter activity was diminished by mutation of a CHOP-binding site of DR5 promoter. Although rottlerin is known to be as an inhibitor of novel isoforms of protein kinase C (PKC), specifically PKC delta, not only suppression of PKC delta expression by siRNA but also overexpression of wild-type-PKC delta or dominant-negative-PKC delta did not affect the rottlerin-mediated induction of DR5 in our study. These results suggest that rottlerin induces upregulation of DR5 via PKC delta-independent pathway. Furthermore, subtoxic dose of rottlerin sensitizes human cancer cells, but not normal cells, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Thus, DR5-mediated apoptosis, which is induced by rottlerin alone or by the combined treatment with rottlerin and TRAIL, may offer a new therapeutic strategy against cancer.

An aromatic imine group enhances the EL efficiency and carrier transport properties of highly efficient blue emitter for OLEDs

This study not only describes the synthesis and characterization of a novel indenofluorene derivative, 6,6,12,12-tetraethyl-2,8-bis-[1,1′;3′,1′]terphenyl-4′-yl-6,12-dihydro-indeno[1,2-b]fluorine (TP-EIF), for use as an emitting material in blue organic light emitting diodes (OLEDs), but also the comparison with 6,6,12,12-tetraethyl-2,8-bis-[1,1′;3′,1′]terphenyl-4′-yl-6,12-dihydro-diindeno[1,2-b;1′,2′-e]pyrazine (TP-EPY). UV-visible and PL spectra showed that the TP-EPY absorption and emission bands were red-shifted with narrow full widths at half maxima (FWHMs) compared to TP-EIF, both in solution and as a film. Density functional theory electronic structure calculations suggested that the spectral differences arose from the electron withdrawing properties of the imine group in the indenopyrazine, which increased conjugation in the core group and decreased conjugation in the side group at the LUMO level. The lower energy of the LUMO in TP-EPY resulted in increased active electron injection in electron-only devices and cyclic voltammetry (CV) measurements. The hole mobilities, which were measured by time of flight (TOF) methods, were 1.8 × 10−3 and 1.1 × 10−4 cm2 V−1 s for TP-EPY and TP-EIF, respectively, which demonstrated that TP-EPY displayed excellent hole transport abilities. The electron mobility was also high in TP-EPY (8.3 × 10−5 cm2 V−1 s). TP-EPY was, therefore, shown to be bipolar, unlike TP-EIF. The electroluminescence (EL) performance of TP-EPY in OLED devices was higher than that of TP-EIF: the luminance efficiencies were 1.72 and 0.76 cd A−1, and the power efficiencies were 0.65 and 0.27 lm W−1, for TP-EPY and TP-EIF, respectively. In particular, the FWHMs of the EL spectral bands were 54 nm for TP-EPY and 73 nm for TP-EIF, which demonstrated enhanced emission spectral purity. The external quantum efficiency of TP-EPY was 5.1%, which was more than twice the value for TP-EIF (2.19%).