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Biomedical subjects

Hidekatsu Yanai

Publications and source records attributed to Hidekatsu Yanai.

14 recordsLinked to original sources
PubMed2006

Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury.

Recanalization and neuroprotection have been mainly targeted for the specific treatment of acute ischemic stroke. Free radicals play a crucial role in brain ischemic injury by exacerbating membrane damage through peroxidation of unsaturated fatty acids of cell membrane, leading to neuronal death and brain edema. Free radicals have been implicated in stroke pathophysiology as pivotal contributors to cell injury. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a novel potent free radical scavenger that has been clinically used to reduce the neuronal damage following ischemic stroke. Edaravone exerts neuroprotective effects by inhibiting endothelial injury and by ameliorating neuronal damage in brain ischemia. Edaravone provides the desirable features of NOS: it increases eNOS (beneficial NOS for rescuing ischemic stroke) and decreases nNOS and iNOS (detrimental NOS). Post- reperfusion brain edema and hemorrhagic events induced by thrombolytic therapy may be reduced by edaravone pretreatment. Increased productions of superoxide and NO in the brain after reperfusion and a concomitant surge in oxygen free radicals with increased NO during recirculation lead to formation of peroxynitrite, a superpotent radical. Edaravone, which inhibits oxidation and enhances NO production derived from increased eNOS expression, may improve and conserve cerebral blood flow without peroxynitrite generation during reperfusion. Clinical experience with edaravone suggests that this drug has a wide therapeutic time window. The combination therapy (a thrombolytic plus edaravone) is likely to target brain edema, reduce stroke death and improve the recovery from neurological deficits in stoke patients.

Animals↗
PubMed2006

The possible contribution of a general glycosphingolipid transporter, GM2 activator protein, to atherosclerosis.

We previously found that oxidized low-density lipoprotein (LDL) elevated the expression of mRNA of GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-Cer (GM2) ganglioside activator protein, in human monocyte-derived macrophages. Recently, GM2 activator protein has become known as a general glycosphingolipid transporter as well as a specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. Accumulation of glycosphingolipids has been observed in the serum or aorta of atherosclerotic model animals and humans. The proliferation of aortic smooth muscle cells, elevation of LDL uptake by macrophages, interfering LDL clearance by the liver, and enhancement of platelet adhesion to collagen have been proposed as the underlying mechanisms of glycosphingolipid-mediated atherogenesis. The GM2 activator protein can bind, solubilize and transport a broad spectrum of lipid molecules, indicating that GM2 activator protein may function as a general intra- and inter-cellular lipid transport protein. Collectively, elevated levels of GM2 activator protein in the aorta may be another feature of human atherosclerosis.

Atherosclerosis↗
PubMed2005

Evaluation of risk for atherosclerosis in Alagille syndrome and progressive familial intrahepatic cholestasis: two congenital cholestatic diseases with different lipoprotein metabolisms.

OBJECTIVES: To evaluate the risk for atherosclerosis in Alagille syndrome (AGS) and progressive familial intrahepatic cholestasis (PFIC) on the basis of lipoprotein metabolism and by ultrasonography. STUDY DESIGN: Five patients with AGS and 5 with PFIC, ages 3 to 4 years, were enrolled. Intimal-medial thickness and wall stiffness of the common carotid artery were examined by ultrasonography. Serum levels of lipids and lipoproteins were determined. Further, the chemical composition of LDL and its ability to transform macrophages into foam cells were determined. RESULTS: Intimal-medial thickness and wall stiffness were increased in patients with PFIC but not in patients with AGS. Total cholesterol, LDL cholesterol, HDL cholesterol, and lipoprotein X were remarkably increased in patients with AGS, whereas in patients with PFIC, an increase in triglyceride and a decrease in HDL cholesterol were the prominent findings. However, despite the normal LDL cholesterol level, oxidized LDL level was strikingly high in patients with PFIC. LDLs from patients with PFIC had high TG contents and exhibited high abilities to transform macrophages into foam cells. CONCLUSIONS: These findings suggest that patients with PFIC are at high risk for cardiovascular disorders involving atherosclerosis.

Alagille Syndrome↗
PubMed2004

Effect of ascorbate on serum lipids and urate metabolism during exhaustive training.

Physical activity is associated with beneficial changes in serum lipids, but exhaustive exercise has been suggested to increase oxidative stress. To test the effect of ascorbate (vitamin C) on serum lipids and the metabolism of urate, which is the most important intrinsic antioxidant, during exhaustive exercise, we performed a randomized, blinded, placebo-controlled study on eight male well-trained athletes. Subjects were randomly allocated to either a group given 1000 mg of ascorbate daily (n=4) or a placebo group (n=4). Fasting serum lipids and urate concentrations were measured before and after 3 weeks of training. Although serum low-density lipoprotein (LDL)-cholesterol levels decreased and high-density lipoprotein (HDL)-cholesterol levels increased significantly in the ascorbate group after the 3 weeks of training, serum LDL-cholesterol levels increased and HDL-cholesterol levels decreased significantly in the placebo group. Furthermore, serum urate levels were elevated significantly in the placebo group; however, these levels did not change in the ascorbate group. When compared with the placebo group, significantly higher serum HDL-cholesterol and lower serum LDL-cholesterol and urate levels were observed in the ascorbate group after training. In conclusion, our results suggested that ascorbate may contribute to the desirable changes in serum lipids during exhaustive training and suggest the significant association between ascorbate and urate under intense training.

Adult↗
PubMed2004

Expression of cholesterol sulfotransferase (SULT2B1b) in human skin and primary cultures of human epidermal keratinocytes.

Cholesterol sulfate is a highly amphipathic molecule that is present in a relatively high concentration in the epidermis of human skin, particularly in the granular layer. The physiologic significance of this finding, however, is not well-understood. Therefore, we examined expression of the gene encoding for the enzyme that sulfonates cholesterol (SULT2B1b). Of the three enzymes known to sulfonate steroids/sterols, only the SULT2B1b isozyme was detected in cultures of normal human epidermal keratinocytes (NHEK) in response to Ca(2+)-induced terminal differentiation as well as by normal human epidermal tissue. Immunocytochemical analysis of normal skin as well as specific skin disorders was carried out. In normal skin, the expression of SULT2B1b was localized to the granular layer of the epidermis similar to that of filaggrin, an acknowledged late marker of differentiation and in contrast to that of involucrin, an early marker of terminal differentiation, which was expressed throughout the suprabasal region. The confinement of SULT2B1b to the granular layer coincides with this being the area with the highest cholesterol sulfate content suggesting that the physiologic action of cholesterol sulfate is likely carried out in this region of the living epidermis. Additionally, 88% of cholesterol sulfate in NHEK was membrane-associated further suggesting a cellular location for cholesterol sulfate action.

Calcium↗
PubMed2003

Expression of cholesterol sulfotransferase (SULT2B1b) in human platelets.

BACKGROUND: Cholesterol sulfate, the most important sterol sulfate in the human circulation, has emerged as a multifaceted molecule. Among its many demonstrated regulatory actions is its ability to influence blood clotting and fibrinolysis. Additionally, cholesterol sulfate is a constituent of human platelets, where it has been shown to support platelet aggregation. METHODS AND RESULTS: We have documented the presence of the enzyme (SULT2B1b) that sulfonates cholesterol in human platelets and examined the influence of plasma lipoproteins on the expression and activity of this enzyme. SULT2B1b mRNA was detected by reverse transcription-polymerase chain reaction and found to be the only steroid/sterol sulfotransferase expressed in these discoid anucleate particles. Using real-time polymerase chain reaction for quantification, we found that the level of SULT2B1b mRNA in platelets was maintained at 4 degrees C but substantially diminished over a period of 4 hours at 37 degrees C. The loss of SULT2B1b mRNA, however, was markedly reduced in the presence of HDL but not LDL. The stabilizing influence of HDL was attributable specifically to its apolipoprotein (apo) A-I component, whereas apoA-II and apoE were without effect. Importantly, there was a direct correlation between platelet SULT2B1b mRNA and protein levels in the presence or absence of lipoprotein that was reflected in enzymatic activity and cholesterol sulfate production. CONCLUSIONS: Human platelets selectively express SULT2B1b, the physiological cholesterol sulfotransferase. Furthermore, the stability of SULT2B1b mRNA and protein in platelets maintained at 37 degrees C is subject to regulation by the apoA-I component of HDL.

Apolipoproteins↗
PubMed2003

Conservation of the hydroxysteroid sulfotransferase SULT2B1 gene structure in the mouse: pre- and postnatal expression, kinetic analysis of isoforms, and comparison with prototypical SULT2A1.

A novel mouse hydroxysteroid sulfotransferase cDNA has been cloned, and organization of its gene structure has been determined. The new mouse sulfotransferase, SULT2B1a, and its closely related isoform, SULT2B1b, are derived from a single SULT2B1 gene as a result of an alternative exon I and differential splicing. Thus, the only structural distinction between the two SULT2B1 isoforms is at their amino-terminal ends. Importantly, in contrast to the prototypical mouse hydroxysteroid sulfotransferase SULT2A1, the SULT2B1 isoforms have a predilection for cholesterol. Real-time RT-PCR reveals that the SULT2B1a isoform is most abundantly expressed in the brain and spinal cord, whereas SULT2B1b and SULT2A1 are weakly, if at all, expressed in the central nervous system. On the other hand, the SULT2B1b isoform is the most prominent hydroxysteroid sulfotransferase expressed in skin, whereas SULT2A1 is strikingly expressed in the liver. The substrate specificities and differential expression patterns of the three SULT2 isozymes strongly suggest that they have distinct biologic roles to play. Of further interest, the mouse SULT2B1 and SULT2A1 genes are differentially expressed during embryonic development, with the former being expressed at all stages from E8.5-E19, whereas the latter is not expressed until E19. It is speculated that, during embryonic development, SULT2B1b is required for production of cholesterol sulfate essential for normal skin development, whereas SULT2B1a produces pregnenolone sulfate, an essential neurosteroid during development of the central nervous system.

Amino Acid Sequence↗
PubMed2002

Unique character and metabolism of high density lipoprotein (HDL) in fetus.

Lipid and lipoprotein profiles, and enzymes for the lipid metabolism were compared between cord and adult blood. Consistent with previous reports, the major lipoprotein in cord blood was high-density lipoprotein (HDL), and that in adult blood was low-density lipoprotein (LDL). The level of apolipoprotein E (apo E) in cord blood was almost equivalent to that in adult blood, while other apolipoproteins and lipids were all lower than the adult level. In cord blood, apo E-rich HDL cholesterol represented more than 30% of total HDL cholesterol (around 11% in adult), and the concentration was about twice of that in adult blood. This apo E-rich HDL cholesterol was poorly esterified (E/T 56%) compared with that in adults (93%). The lecithin:cholesterol acyltransferase (LCAT) activity in cord blood was extremely low, while the activity and mass of cholesteryl ester transfer protein (CETP) were higher than those in adult blood. The apo E genotype did not show influences on total cholesterol, LDL cholesterol, total HDL cholesterol, and apo E rich HDL cholesterol levels in cord blood, as opposed to those in adult blood. The association of D442G mutation of the CETP gene with the increased HDL cholesterol in adult blood was not seen in cord blood. Rather, the mutation was associated with low total cholesterol and LDL cholesterol levels in cord blood. These results indicate that, in fetus, the character and metabolism of HDL, especially of apo E-rich HDL cholesterol, are distinct from those in adults.

Adult↗