Cytosolic estrogen sulfotransferase (SULT1E1) mainly catalyzes the sulfoconjugation and deactivation of estrogens that are known to exert potent anti-atherogenic effects. However, it remains unknown ...about the connection between SULT1E1 and atherosclerosis. Recently, we reported that SULT1E1 is highly expressed in the aorta with plaques of high fat-fed ApoE knockout (KO) mice (mouse model of atherosclerosis), and interacts with oxidized low-density lipoprotein (Ox-LDL) known as a major component of atherosclerotic lesions. In this study, immunohistochemical staining for SULT1E1 in the aorta of high fat-fed ApoE KO mice showed that SULT1E1 is detected in vascular endothelial cells overlying atherosclerotic plaques. Results from Western blotting showed that Ox-LDL induces the protein expression of both SULT1E1 and peroxisome proliferator-activated receptor (PPAR) γ in human umbilical vein endothelial cells (HUVECs), and then that a PPARγ antagonist GW9662, but not a PPARα antagonist GW6471, inhibited the protein expression of SULT1E1 induced by Ox-LDL. Moreover, GW9662 significantly increased the proliferation of HUVECs induced by Ox-LDL. Our results suggest that SULT1E1 and PPARγ, both of which are increased by Ox-LDL, may interact with each other, and then may reduce cooperatively Ox-LDL-induced proliferation of vascular endothelial cells overlying atherosclerotic plaques, leading to against atherosclerosis.
Cytosolic estrogen sulfotransferase (SULT1E) mainly catalyzes the sulfate conjugation of estrogens, which decrease atherosclerosis progression. Recently we reported that a YKEG sequence in human ...SULT1E1 (hSULT1E1) corresponding to residues 61–64 can bind specifically to oxidized low-density lipoprotein (Ox-LDL), which plays a major role in the pathogenesis of atherosclerosis; its major oxidative lipid component lysophosphatidylcholine (LPC), and its structurally similar lipid, platelet-activating factor (PAF). In this study, we investigated the effect of Ox-LDL on the sulfating activity of hSULT1E1.
In vivo
experiments using a mouse model of atherosclerosis showed that the protein expression of SULT1E1 was higher in the aorta of mice with atherosclerosis compared with that in control animals. Results from a sulfating activity assay of hSULT1E1 using 1-hydroxypyrene as the substrate demonstrated that Ox-LDL, LPC, and PAF markedly decreased the sulfating activity of hSULT1E1, whereas native LDL and 1-palmitoyl-2-(5′-oxo-valeroyl)-
sn
-glycero-3-phosphocholine (POVPC) as one of the oxidized phosphatidylcholines showed the opposite effect. The sulfating activity greatly changed in the presence of LPC, PAF, and POVPC in their concentration-dependen manner (especially above their critical micelle concentrations). Moreover, Ox-LDL specifically recognized dimeric hSULT1E1. These results suggest that the effects of Ox-LDL and native LDL on the sulfating activity of hSULT1E1 might be helpful in elucidating the novel mechanism underlying the pathogenesis of atherosclerosis, involving the relationship between estrogen metabolism, LDL, and Ox-LDL.
Estrogen sulfotransferase (SULT1E) mainly catalyzes the sulfation of estrogens, which are known to prevent the pathogenesis of atherosclerosis. Recently, we found that peptides with a YKDG sequence ...specifically bind to oxidized low‐density lipoprotein (Ox‐LDL), which plays a major role in the pathogenesis of atherosclerosis. Here, we investigated the interaction between human SULT1E1 (hSULT1E1), which has a YKEG sequence (residues 61–64) unlike other human SULTs, and Ox‐LDL. Results from polyacrylamide gel electrophoresis and western blotting demonstrated that hSULT1E1 specifically binds to Ox‐LDL and its major lipid component (lysophosphatidylcholine; LPC), and platelet‐activating factor (PAF), which bears a marked resemblance to LPC in terms of structure and activity. Moreover, an N‐terminally fluorescein isothiocyanate (FITC)‐labeled decapeptide (MIYKEGDVEK; FITC‐hSULT1E1‐P10) corresponding to residues 59–68 of hSULT1E1 specifically binds to Ox‐LDL, LPC, and PAF. Unveiling the specific interaction between hSULT1E1 and Ox‐LDL, LPC, and PAF provides important information regarding the mechanisms underlying various diseases caused by Ox‐LDL, LPC, and PAF, such as atherosclerosis. In addition, FITC‐hSULT1E1‐P10 could be used as an efficient fluorescent probe for the detection of Ox‐LDL, LPC, and PAF, which could facilitate the mechanistic study, identification, diagnosis, prevention, and treatment of atherosclerosis.
Human estrogen sulfotransferase (hSULT1E1) and its related fluorescein isothiocyanate (FITC)‐labeled decapeptide (FITC‐hSULT1E1‐P10) specifically bind to oxidized LDL (Ox‐LDL), its major lipid component (LPC), and platelet‐activating factor (PAF). These interactions could provide important information regarding the mechanisms underlying hSULT1E1, Ox‐LDL, LPC, and PAF‐related various diseases. FITC‐hSULT1E1‐P10 may be useful as a fluorescent probe for efficient detection of Ox‐LDL, LPC, and PAF.
Platelet-activating factor (PAF) is an important mediator of allergic reactions such as anaphylaxis, and is therefore an anaphylactic drug target. Previously, we found marked inhibition of ...anaphylactic reactions by a synthetic N-terminally biotinylated peptide (BP21) capable of specifically binding PAF. In this study, we investigated the effects of 10-hydroxy-2-decenoic acid (10-HDA) and various peptides derived from royalisin, both of which are widely known to be major components of royal jelly from honeybees, on PAF/histamine-induced rat hind-paw edema and mouse anaphylactic hypothermia. In a rat model of hind paw edema, both 10-HDA (50 nmol/paw) and a royalisin-related N-terminally biotinylated peptide, Biotin-RL-Y11, (10 nmol/paw) markedly inhibited PAF-induced paw edema by 95.5±5.0% and 71.9±9.9%, respectively. 10-HDA also inhibited histamine-induced paw edema by 42.7±19.2%. In contrast, three peptides with N-terminal HDA modifications, namely 10-HDA-RL-Y11, 10-HDA-RL-R11, and 10-HDA-P21 only weakly inhibited PAF-induced paw edema. In a mouse model of anaphylaxis, the administration of 10-HDA (100-1000 nmol/mouse) and/or Biotin-RL-Y11 (100 nmol/mouse) showed the inhibitory effects on anaphylactic hypothermia. These results suggest that both 10-HDA and Biotin-RL-Y11 may exert an anti-anaphylactic effect targeting PAF.
Movements of knee joints are relative motions between tibia and femur, which include rolling and sliding. Conventional wearable knee assistive device utilized a hinge joint and generates ...nonnegligible mismatched motions under deep flexions. To assist the knee motion including the deep flexion, we have developed several types of the biomimetic knee joint (BKJ) mechanism that mimics the rotational centers of biological knees. A polycentric BKJ which is a polycentric joint structure that mimics the rollback motions of knee joints by combining two gears with different radii is used in this study. From a viewpoint of the complexity of the device, the passive devices have a significant advantage. However, a lack of the automatic adjustment function is a big disadvantage. To enhance the usability and applicational field, we propose the Semi-active Knee Joint (SKJ) in this study. The SKJ has a polycentric gear mechanism and linear motion springs. In addition, the spring constant is adjustable from a weak spring to a strong spring. The basic mechanism, design method, and design processes are reported in this paper. As a result of an optimal design of the gear system based on the measurement result of a knee joint motion for a subject, we adequately designed a pair of gears for a tailer made SKJ with small misalignment of less than 5 mm even in the deep flexion over 90°. In addition, non-linear function of the assistive torque was analyzed for a mechanical model. As a result, spring constant, k is decided to be 45 N/mm for the upper knee and 20 N/mm for the lower knee.
The aim of this paper is to consider the problems faced by a multi-purpose public hall that arranges it's own activities. In the case of Nagoya City Arts Center, activity management itself must be ...well appreciated. But because the resources of the hall are limited, this positive attitude to cope with various needs brings up another dilemma. In order to elucidate it's role and to elaborate the effective operational strategies, it is necessary to conduct more detailed studies focused on the open network of creative activities in the region.
This study aims to investigate the state of the management of Chinese theatres and theater companies. The findings of the study are surmerized as follows: 1) Governmental subsidy of theatres and ...companies has diminished relatively and yet company members are guaranteed to keep the minimum standard of living. 2) Theatres have been required to be self-supportive. So recently multi-purpose halls and complexes have been constructed. Some theaters have tended to ignore technical maintenance due to financial difficulty. 3) The performances produced by members crossing over each company has been introduced and in these situation the infrastructure for theatrical activity provided by government are useful.
The aim of this study is to understand the relationship between sites of theatres and urban form under the socialist system. We analysed the sites and distribution of 251 theatres in Peiking and ...Shianghai according to the investigating and hearing. We realized the following items: 1) From a visual point of urban form, theatres have three types which are (1) the theatres in the street, (2) the halls in the area of working groups and (3) the theatres in the housing estates. 2) Now many problems have been appearing about the theatres and halls of (2) and (3).
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