Rashba Effect in Functional Spintronic Devices.

Exploiting spin transport increases the functionality of electronic devices and enables such devices to overcome physical limitations related to speed and power. Utilizing the Rashba effect at the interface of heterostructures provides promising opportunities toward the development of high-performance devices because it enables electrical control of the spin information. Herein, the focus is mainly on progress related to the two most compelling devices that exploit the Rashba effect: spin transistors and spin-orbit torque devices. For spin field-effect transistors, the gate-voltage manipulation of the Rashba effect and subsequent control of the spin precession are discussed, including for all-electric spin field-effect transistors. For spin-orbit torque devices, recent theories and experiments on interface-generated spin current are discussed. The future directions of manipulating the Rashba effect to realize fully integrated spin logic and memory devices are also discussed.

Field-free switching of perpendicular magnetization through spin-orbit torque in antiferromagnet/ferromagnet/oxide structures.

Spin-orbit torques arising from the spin-orbit coupling of non-magnetic heavy metals allow electrical switching of perpendicular magnetization. However, the switching is not purely electrical in laterally homogeneous structures. An extra in-plane magnetic field is indeed required to achieve deterministic switching, and this is detrimental for device applications. On the other hand, if antiferromagnets can generate spin-orbit torques, they may enable all-electrical deterministic switching because the desired magnetic field may be replaced by their exchange bias. Here we report sizeable spin-orbit torques in IrMn/CoFeB/MgO structures. The antiferromagnetic IrMn layer also supplies an in-plane exchange bias field, which enables all-electrical deterministic switching of perpendicular magnetization without any assistance from an external magnetic field. Together with sizeable spin-orbit torques, these features make antiferromagnets a promising candidate for future spintronic devices. We also show that the signs of the spin-orbit torques in various IrMn-based structures cannot be explained by existing theories and thus significant theoretical progress is required.

Chronic idiopathic macrocheilia associated with simple lip enlargement and salivary gland hyperplasia.

Chronic macrocheilia is a relatively rare condition of chronic lip enlargement. It can be cosmetically and functionally problematic, and often poses a diagnostic and therapeutic challenge to clinicians especially when its etiology is unclear. We describe a 40-year-old Korean man who presented with a 4-year history of lower lip swelling and was diagnosed as having chronic idiopathic macrocheilia after excluding other disease entities based on histopathological and clinical findings. We believe that the present case has a unique clinico-histopathological feature that differentiates it from other cases of chronic cheilitis, namely, simple lip swelling showing minor salivary gland hyperplasia only, suggesting the possibility of a new disease entity.

Glutathione prevented dopamine-induced apoptosis of melanocytes and its signaling.

BACKGROUND: Dopamine (DA), a monoamine neurotransmitter, is a well-known neurotoxin and plays an etiologic role in neurodegenerative disorders such as Parkinson's disease. DA exerts its toxic effect by generation of reactive oxygen species and quinone product. Vitiligo, a depigmentary disorder of the skin and hair characterized by selective destruction of melanocytes, has been reported to show increased levels of DA with onset and progression of the disease. OBJECTIVE: The aim of this study is to investigate the cytotoxic effect of DA on melanocytes and to search for protective antioxidants against DA-induced toxicity. In addition, molecular mechanism of cell death was also investigated. METHODS: Cells were treated with DA and cell viabilities were measured by crystal violet staining method. To investigate the cytoprotective activity of various antioxidants, vitamin C, vitamin E, Trolox, quercetin, N-acetylcysteine (NAC) and l-glutathione (GSH) were used. To study cytoprotective effects of NAC and GSH, Mel-Ab cells and cultured normal human melanocytes were pretreated with NAC or GSH, then DA solution was added. DA-induced apoptosis and activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) were also observed by flow cytometric analysis and Western blotting. RESULTS: The viability of DA-treated Mel-Ab cells significantly decreased in a dose-dependent manner while keratinocytes were much more resistant to DA-toxicity, which was a consistent finding with the selective melanocyte loss observed in vitiligo. Among various antioxidants used in this study, only thiol-containing antioxidants such as NAC or GSH inhibited both JNK and p38 MAPK activation and apoptosis, indicating the unique protective capacity of thiol compounds. Cultured normal human melanocytes were also susceptible to DA and thiol compounds were very efficiently protective against DA-induced cytotoxicity. CONCLUSION: DA-induced apoptosis and cytoprotective effect of thiol compounds shown in this study could be a clue to understand pathogenesis of viltigo and provide a new therapeutic strategy.

Application of a pigment measuring device--Mexameter--for the differential diagnosis of vitiligo and nevus depigmentosus.

BACKGROUND/PURPOSE: Vitiligo and nevus depigmentosus (ND) present similar hypopigmented macules with significantly different prognoses. Although the distinction between the two diseases is important, differential diagnosis relies on medical history and physical examination, which is far from decisive in some cases. The Mexameter is an objective skin color-measuring device, and has been reported to provide a reproducible and sensitive means of quantifying small skin color differences. In this study, we investigated the usefulness of a Mexameter for discriminating these diseases. METHODS: A selection of 202 hypopigmented skin lesions (182 from vitiligo and 20 from ND) were the objects of this study. Using a Mexameter, MIs were obtained from lesions and symmetrically located control skin. RMIs, ratios of the MIs of lesional skins to control skins, were calculated. RESULTS: The mean MIs and RMIs were significantly different for vitiligo and ND. The mean RMI of ND lesions was 74+/-13, which was significantly higher than that of vitiligo lesions (50+/-24). No ND lesion had an RMI of <50%. CONCLUSION: This study shows that the Mexameter, an objective pigment-measuring device, can be used to achieve a more accurate diagnosis of hypopigmentary disorders, and that the relative melanin index (RMI), which represents the relative pigment levels, might be a more effective parameter than the melanin index (MI) itself for comparing pigmentation differences.

Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes.

Sphingosylphosphorylcholine (SPC) is emerging as a potent signaling-lipid mediator. In this study, we investigated the effects of SPC on melanogenesis using cultured human melanocytes. Our results show that SPC significantly inhibits melanin synthesis in a concentration-dependent manner, and further that it reduces the activity of tyrosinase, the rate-limiting melanogenic enzyme. SPC treatment was also found to induce short-thick dendrites in human melanocytes, but not to reduce tyrosinase activity in a cell-free system, whereas kojic acid directly inhibited tyrosinase. These results suggest that SPC reduces pigmentation by indirectly regulating tyrosinase. In further experiments, SPC was found to downregulate microphthalmia-associated transcription factor (MITF) and tyrosinase, and Western blotting showed that SPC induces the activations of extracellular signal-regulated kinase (ERK) and 90 kDa ribosomal S6 kinase (RSK-1). Moreover, the specific ERK pathway inhibitor, PD98059, blocked the hypopigmentation effect of SPC, and abrogated the SPC-mediated downregulation of MITF. These results suggest that the ERK pathway is involved in the melanogenic signaling cascade, and that ERK activation by SPC reduces melanin synthesis via MITF downregulation.

Cytoprotective effect of green tea extract and quercetin against hydrogen peroxide-induced oxidative stress.

In this study, we evaluated the cytoprotective effects of antioxidative substances in hydrogen peroxide (H2O2) treated Mel-Ab melanocytes. Tested substances include selenium, quercetin, green tea (GT) extract, and several vitamins (ascorbic acid, Trolox, and folic acid). Of these, both quercetin and GT extract were found to have strong cytoprotective effects on H2O2-induced cell death. We also examined additive effects, but no combination of two of any of the above substances was found to act synergistically against oxidative damage in Mel-Ab cells. Nevertheless, a multi-combination of GT extract, quercetin, and folic acid appeared to prevent cellular damage in a synergistic manner, which suggests that combinations of antioxidants may be of importance, and that co-treatment with antioxidants offers a possible means of treating vitiligo, which is known to be related to melanocyte oxidative stress.

Protective effects of EGCG on UVB-induced damage in living skin equivalents.

In this study, we evaluate the effects of (-)-epigallocatechin-3-gallate (EGCG) on ultraviolet B (UVB)-irradiated living skin equivalents (LSEs). Histologically, UVB irradiation induced thinning of the LSE epidermis, whereas EGCG treatment led to thickening of the epidermis. Moreover, EGCG treatment protected LSEs against damage and breakdown caused by UVB exposure. Immunohistochemically, UVB-exposed LSEs expressed p53, Fas, and 8-hydroxy-deoxyguanosine (8-OHdG), all of which are associated with apoptosis. However, EGCG treatment reduced the levels of UVB-induced apoptotic markers in the LSEs. In order to determine the signaling pathways induced by UVB, Western blot analysis was performed for both c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), which are associated with UVB-induced oxidative stress. UVB activated JNK in the epidermis and dermis of the LSEs, and EGCG treatment reduced the UVB-induced phosphorylation of JNK. In addition, p38 MAPK was also found to have increased in the UVB-exposed LSEs. Also, EGCG reduced levels of the phosphorylation of UVB-induced p38 MAPK. In conclusion, pretreatment with EGCG protects against UVB irradiation via the suppression of JNK and p38 MAPK activation. Our results suggest that EGCG may be useful in the prevention of UVB-induced human skin damage, and LSEs may constitute a potential substitute for animal and human studies.

Heat treatment decreases melanin synthesis via protein phosphatase 2A inactivation.

In the present study, we investigated the effects of heat treatment on melanogenesis in a mouse melanocyte cell line (Mel-Ab). It has been reported that activated extracellular signal-regulated kinase (ERK) is responsible for microphthalmia-associated transcription factor (MITF) degradation, which leads to a reduction in tyrosinase protein production and melanin synthesis. Here we demonstrate that heat treatment induces sustained ERK activation, which may inhibit melanogenesis. However, the specific ERK pathway inhibitors, PD98059 or U0126 did not restore heat-induced hypopigmentation. Furthermore, PD98059 or U0126 hardly blocked the heat-induced activation of ERK. These results suggest that heat treatment may inactivate protein phosphatase, and thus ERK activation is maintained. To support this hypothesis, we examined the effects of heat treatment on protein phosphatase 2A (PP2A) activity. The results obtained show that heat treatment inactivates PP2A, which may subsequently cause ERK activation and that heat treatment inhibits MITF promoter activity. Overall, our results demonstrate that heat treatment reduces melanin production in a temperature-dependent manner.

Lysophosphatidic acid inhibits melanocyte proliferation via cell cycle arrest.

Lysophosphatidic acid (LPA) is a well-known mitogen in various cell types. However, we found that LPA inhibits melanocyte proliferation. Thus, we further investigated the possible signaling pathways involved in melanocyte growth inhibition. We first examined the regulation of the three major subfamilies of mitogen-activated protein (MAP) kinases and of the Akt pathway by LPA. The activations of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) were observed in concert with the inhibition of melanocyte proliferation by LPA, whereas p38 MAP kinase and Akt were not influenced by LPA. However, the specific inhibition of the ERK or JNK pathways by PD98059 or D-JNKI1, respectively, did not restore the antiproliferative effect. We next examined changes in the expression of cell cycle related proteins. LPA decreased cyclin D1 and cyclin D2 levels but increased p21(WAF1/CIP1) (p21) and p27KIP1 (p27) levels, which are known inhibitors of cyclin-dependent kinase. Flow cytometric analysis showed the inhibition of DNA synthesis by a reduction in the S phase and an increase in the G0/G1 phase of the cell cycle. Our results suggest that LPA induces cell cycle arrest by regulating the expressions of cell cycle related proteins.