Search PubMed⌕ Search

Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 37 records · Page 2Linked to original sources
PubMed2005

Fatigue-related changes in discharge patterns of motor units in the inferior head of the lateral pterygoid muscle in humans.

OBJECTIVE: To investigate single motor unit (SMU) firing patterns of the inferior head of the human lateral pterygoid muscle (IHLP) during sustained isometric contractions, and to examine IHLP fatigability. DESIGN: In 5 subjects, EMG was recorded from the right IHLP during generation of horizontal isometric mandibular force towards left side. Subjects tracked a target on an oscilloscope, slowly increasing the force to 25% of maximum voluntary contraction, and then maintained that force for 120 s (endurance task). Subjects rested for 30 s after each test, and three 10s recovery tests were performed every 30 s (recovery task). Fatigue data were obtained from 23 SMUs. RESULTS: Twelve of 23 SMUs (52.2%) continued to fire throughout the 120 s, and each subject had at least one of these units. These units were classified as tonic pattern (T-unit). The firing rate of 6 of the 12 T-units (50.0%) decreased gradually with time. Comparison of the mean firing rate and coefficient of variance (CV) of interspike interval (ISI) of the 12 T-units between pre-fatigue, post-fatigue and the three recovery tasks showed that the mean firing rate decreased and CV of ISI increased after fatigue. Mean firing rate and CV of ISI recovered after 30 s of rest after the endurance task. CONCLUSIONS: The firing patterns of IHLP units changed with the passing of time during sustained isometric contractions leading to fatigue.

Action Potentials↗
PubMed2005

Unique atheroprotective property of azelnidipine, a dihydropyridine-based calcium antagonist.

Insulin resistance and central obesity are often associated with hypertension. The metabolic syndrome is a cluster of these common clinical disorders, and is related with an increased risk for cardiovascular diseases. A number of pro-inflammatory cytokines derived from adipose tissues have been thought to contribute to the development of insulin resistance and accelerated atherosclerosis. Among them, TNF-alpha has been most widely studied; it not only suppresses the insulin signaling, but also elicits vascular inflammation. Indeed, inhibition of TNF-alpha was found to improve insulin resistance in obese rats and reduce the progression of atherosclerosis in apolipoprotein E knockout mice, respectively. These observations demonstrate that TNF-alpha could play a central role in the pathogenesis of insulin resistance and accelerated atherosclerosis in the metabolic syndrome. Considering that the primary goals of treatment for hypertensive patients with the metabolic syndrome are prevention of the development of diabetes and cardiovascular events, anti-hypertensive drugs that have abilities to block the TNF-alpha signaling would be desirable as a first-line therapy for these patients. In the process of the search for such a unique anti-hypertensive drug, we have recently found that azelnidipine, a newly developed and commercially used long-acting dihydropyridine-based calcium antagonist (DHP), inhibited TNF-alpha-induced activator protein-1 activation and interleukin-8 expression in human umbilical vein endothelial cells by suppressing NADPH oxidase-mediated reactive oxygen species generation. The concentration of azelnidipine that was found effective in these in vitro-experiments is well within the therapeutic range. Since endothelial cells do not possess voltage-operated L-type calcium channels, these observations suggest that the beneficial effects of azelnidipine are not likely due to calcium channel blocking property, but due to its unique anti-oxidative ability. Furthermore, we have very recently found that serum levels of monocyte chemoattractant protein-1, a biomarker for subclinical atherosclerosis, were significantly decreased by the treatment of azelnidipine in patients with essential hypertension. In this paper, we would like to hypothesize that due to its unique TNF-alpha signal modulatory, anti-oxidative property, azelnidipine may be a promising DHP that targets diabetes and cardiovascular diseases in hypertensive patients with the metabolic syndrome.

Antihypertensive Agents↗
PubMed2005

Expression and distribution of monocarboxylate transporter 1 (MCT1) in the gastrointestinal tract of calves.

In the present study the expression and distribution of monocarboxylate transporter 1 (MCT1) along the gastrointestinal tract (rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum and colon) of calves were investigated on both mRNA and protein levels. The expression of MCT1 protein and its distribution were determined by Western blotting and immunohistochemical staining, respectively by using antibody for MCT1. MCT1 protein was visualized as a 43-kDa band on immunoblots of the membrane proteins prepared from the various regions examined, and it was more highly expressed in forestomach and large intestine than in abomasum and small intestine. With the use of reverse transcriptase-polymerase chain reaction, mRNA encoding for MCT1 was demonstrated in the different tissues examined. The immunohistochemical study confirmed the Western blot findings and showed strong MCT1 immunopositive staining in the stratified squamous epithelia of the forestomach as well as the epithelial cells lining the digestive tract in the cecum, proximal colon, and distal colon. The results suggest that MCT1 may play a role in the transport of SCFA and their metabolites in the gastrointestinal tract of bovines.

Amino Acid Sequence↗
PubMed2005

Clinical significance of enhancer of zeste homolog 2 expression in colorectal cancer cases.

INTRODUCTION: Enhancer of zeste homolog 2 (EZH-2) is a polycomb group (PcG) protein, and the clinical significance of this protein has not yet been determined in colorectal cancer (CRC) cases. Recently, investigations of CRC cases have focused on the interaction between EZH-2 and histone deacetylase-1 (HDAC-1). PATIENTS AND METHODS: We performed real time RT-PCR to evaluate the expression of EZH-2 mRNA quantitatively in tumour and normal tissue samples from 61 cases of CRC. The expression of HDAC-1 in CRC cases was also examined in order to compare its levels with those of EZH-2. RESULTS: Among the CRC cases, 32 patients whose tumour tissue showed overexpression of EZH-2 also had a significantly worse prognosis than did 29 patients whose tumour tissue showed low EZH-2 expression (p<0.05). In addition, a significant correlation between EZH-2 and HDAC-1 expression was observed in 61 CRC cases (p<0.05). Moreover, 20 cases of both high EZH-2 and high HDAC-1 expression showed poor prognoses than did 19 cases in which there was low EZH-2 and low HDAC-1 expression (p<0.05). CONCLUSION: The abundant expression of EZH-2 in CRC cases indicated that EZH-2 may be an oncogene and a prognostic marker for CRC cases. We discovered there was concordant expression of HDAC-1 with EZH-2 in clinical CRC cases, in addition to the fact that higher expression levels of both genes predicted a poor prognosis.

Colorectal Neoplasms↗
PubMed2005

Roles of volume-sensitive Cl- channel in cisplatin-induced apoptosis in human epidermoid cancer cells.

The anti-cancer drug cisplatin induces apoptosis by damaging DNA. Since a stilbene-derivative blocker of Cl-/HCO3- exchangers and Cl- channels, SITS, is known to induce cisplatin resistance in a manner independent of intracellular pH and extracellular HCO3-, we investigated the relation between cisplatin-induced apoptosis and Cl- channel activity in human adenocarcinoma KB cells. A stilbene derivative, DIDS, reduced cisplatin-induced caspase-3 activation and cell death, which were detected over 18 h after treatment with cisplatin. DIDS was also found to reduce sensitivity of KB cells to 5-day exposure to cisplatin. Whole-cell patch-clamp recordings showed that KB cells functionally express volume-sensitive outwardly rectifying (VSOR) Cl- channels which are activated by osmotic cell swelling and sensitive to DIDS. Pretreatment of the cells with cisplatin for 12 h augmented the magnitude of VSOR Cl- current. Thus, it is concluded that cisplatin-induced cytotoxicity in KB cells is associated with augmented activity of a DIDS-sensitive VSOR Cl- channel and that blockade of this channel is, at least in part, responsible for cisplatin resistance induced by a stilbene derivative.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2005

Minimally invasive plate osteosynthesis for comminuted fractures of the metaphysis of the radius.

Five comminuted and displaced fractures of the distal metaphysis of the radius were treated by a technique of minimally invasive plate osteosynthesis (MIPO) with the aim of minimizing soft tissue damage and devascularization of the fracture fragments. This technique used the small AO T-shaped locking compression plate (AO LCP T-plate) and left the pronator quadratus intact. Radial inclination, palmar tilt, and ulnar variance were restored without loss of reduction in all five cases and the fractures healed at an average of 10 weeks, with good to excellent clinical outcomes.

Adult↗
PubMed2005

Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients.

Colorectal cancer is a major public health problem, being the second most common cause of cancer in developed countries. Several epidemiological studies have reported moderately increased risks of colorectal cancer in diabetic patients compared with general population. However, the underlying molecular link between diabetes and colorectal cancer remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs-RAGE interactions stimulated the growth of human pancreatic cancer cells through the autocrine induction of platelet-derived growth factor-B. Furthermore, we have recently found that AGEs stimulated the growth and migration of cultured human melanoma cells and that anti-RAGE antibodies inhibited tumor formation and lung metastasis of melanoma cell xenografts and subsequently improved survival in athymic mice. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and colorectal cancer. In this paper, we would like to propose the possible ways of testing our hypotheses. Is elevation of serum AGE levels a risk factor for colorectal cancer in patients with diabetes? Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for colorecetal cancer in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for colorectal cancer as well? Furthermore, are increased levels of AGEs and RAGE in colorectal cancer associated with poor prognosis in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and colorectal cancer.

Adenocarcinoma↗
PubMed2005

Serum or cerebrospinal fluid levels of glyceraldehyde-derived advanced glycation end products (AGEs) may be a promising biomarker for early detection of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in developed countries. AD is characterized pathologically by the presence of senile plaques and neurofibrillary tangles (NFTs), the major constituents of which are the amyloid beta protein (Abeta) and tau protein, respectively. Several epidemiological studies have reported moderately increased risks of AD in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. Recent understandings of this process have confirmed that AGEs - their receptor (RAGE) interactions may play a role in the pathogenesis of diabetic vascular complications and neurodegenerative disorders including AD. Indeed, it has been demonstrated that AGEs can be identified immunohistochemically to be present in both senile plaques and NFTs from patients with AD. Glycation of Abeta markedly enhances its aggregation in vitro, and the glycation of tau, in addition to hyperphosphorylation, appears to enhance the formation of paired helical filaments. Further, RAGE has been found a specific cell surface receptor for Abeta peptite, thus eliciting neuronal cell perturbation. The active participation of RAGE in the pathogenesis of AD has also been confirmed in RAGE-overexpressed transgenic mice. Moreover, we have recently found that glyceraldehyde-derived AGEs, one of the representative ligands for RAGE, exerted cytopathic effects on cultured neuronal cells and that neurotoxic effect of diabetic serum was completely blocked by neutralizing antibodies against glyceraldehydes-derived AGEs. These observations led us to hypothesize that serum or cerebrospinal fluid (CSF) levels of glyceraldehyde-derived AGEs could become a promising biomarker for early detection of AD. We also would like to propose the possible ways of testing our hypothesis. Are the concentrations of glyceraldehyde-derived AGEs in serum or CSF elevated early in the course of dementia? Are these levels correlated with disease severity and progression, especially in patients with diabetes? These clinical studies clarify whether use of serum or CSF levels of glyceraldehyde-derived AGEs as a biomarker for AD might enable more effective diagnosis and treatment of patients with this devastating disorder.

Alzheimer Disease↗
PubMed2005

Met72Thr polymorphism of pigment epithelium-derived factor gene and susceptibility to age-related macular degeneration.

Age-related macular degeneration (ARMD) is the most common cause of acquired blindness among the people of occupational age. Although the pathogenesis of ARMD is not fully understood, several studies suggest a possible contribution of a genetic factor in the development and progression of ARMD. Pigment epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily of serine protease inhibitors, was first purified from the conditioned media of human retinal pigment epithelial cells as a factor with potent neuronal differentiating activity in human retinoblastoma cells. Recently, PEDF has been shown to be a highly effective inhibitor of angiogenesis in cell culture and animal models. In addition, PEDF has been found in the vitreous, and its levels were decreased in angiogenic eye diseases, thus suggesting that a loss of PEDF in the eye is functionally important in the pathogenesis of ARMD. A functional amino acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) at codon 72 in exon 3 (T/C polymorphism) of the PEDF gene, that results in the formation of BsstSI restriction site, has recently been identified. Since it is well known that a single nucleotide polymorphism and resultant amino acid change often alters the activity or expression level of the target protein, we would like to propose here a novel hypothesis that the Met72Thr polymorphism (T/C polymorphism) of PEDF gene may be a genetic marker for ARMD. Are genotype and allele frequencies of the Met72Thr polymorphism (T/C polymorphism) different between the patients with or without ARMD? Is this polymorphism associated with disease severity and progression? If the answer is yes, does this Met72Thr polymorphism regulate the vitreous levels of PEDF? These clinical studies could provide us with information whether this genetic variant of the PEDF gene could present an attractive candidate susceptibility gene for ARMD.

Amino Acid Substitution↗
PubMed2005

Acarbose is a promising therapeutic strategy for the treatment of patients with nonalcoholic steatohepatitis (NASH).

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, and diabetes. There is a growing body of evidence to show that nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of insulin resistant patients with the metabolic syndrome. Indeed, insulin resistance increases adipocyte lipolysis and subsequently elevates circulating free fatty acids, thus stimulating the accumulation of fatty acids in the liver (hepatic steatosis). Fatty acids elicit reactive oxygen species generation, thereby promoting disease progression to NASH by both lipid peroxidation and inflammatory cytokine production. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, also induces oxidative stress generation, being involved in dysfunction of pancreatic beta cells and vascular wall cells in the metabolic syndrome. Recently, STOP-NIDDM trial revealed that acarbose (Glucobay), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes and newly diagnosed hypertension in patients with impaired glucose tolerance. In this study, acarbose treatment was also found to reduce body mass index and waist circumference in these patients. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose improved triglyceride levels, body weight and systolic blood pressure and subsequently prevented myocardial infarction in type 2 diabetic patients. Since acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion, the beneficial aspects of acarbose could be ascribed to improvement of insulin sensitivity in these patients. Given the pathological link between NASH and insulin resistance, we would like to hypothesize here that acarbose may become a promising therapeutic strategy for the treatment of patients with NASH. Does acarbose treatment improve steatohepatitis histologically? Is the extent of histological improvement by acarbose parallel to that of insulin sensitivity in these patients? Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of progression of liver diseases in patients with NASH.

Acarbose↗
PubMed2005

Therapeutic potentials of unicellular green alga Chlorella in advanced glycation end product (AGE)-related disorders.

Reducing sugars can react non-enzymatically with amino groups of protein to form Amadori products. These early glycation products undergo further complex reaction such as rearrangement, dehydration, and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs in various tissues has been known to progress at an accelerated rate under hyperglycemic conditions in diabetes. Recent understanding of this process has revealed that AGEs have been implicated in the development of many of the pathological sequelae of diabetes and aging, such as atherosclerosis and diabetic microangiopathy. Furthermore, recently, AGE-their receptor (RAGE) interaction was also involved in neurodegenerative diseases, melanoma growth, expansion and metastasis. These observations suggest that blockade of AGE formation may be a novel promising target for therapeutic intervention in these devastating AGE-related disorders. We have recently found that unicellular green alga Chlorella inhibited the formation of AGEs in vitro. Since several lines of evidence have shown anti-atherogenic effects of Chlorella on animal models, we hypothesize here that the beneficial aspects of Chlorella on atherosclerosis could be ascribed, at least in part, to its AGE inhibitory property and that Chlorella may have therapeutic potentials in treatment of patients with other AGE-related disorders such as diabetic microangiopathy and Alzheimer's disease. In this paper, we would like to propose the possible ways of testing our hypotheses. Does daily intake of Chlorella reduce the risk of the incidence and progression of diabetic vascular complications including atherosclerosis? Does Chlorella treatment prevent the development of Alzheimer's disease and/or improve the cognitive impairment of patients with this disorder? If the answers are yes, are plasma or tissue levels of AGE in these patients actually suppressed by Chlorella treatment? And, does the extent of the AGE reduction by Chlorella predict the beneficial effects of Chlorella on these disorders? These prospective studies will provide further valuable information whether blockade by Chlorella of the AGE formation could be clinically relevant.

Administration, Oral↗
PubMed2005

Possible participation of advanced glycation end products in the pathogenesis of osteoporosis in diabetic patients.

Osteoporosis, one of the most prevalent metabolic bone diseases in developed countries, is a major public health problem through its association with fragility fractures. Several epidemiological studies have reported moderately increased risks of osteoporotic bone fractures in diabetic patients compared with general population. However, the underlying molecular link between diabetes and osteoporosis remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells. Furthermore, we have recently found that AGEs-RAGE interactions induced human mesenchymal stem cell apoptosis and subsequently prevented cognate differentiation into adipose tissue, cartilage, and bone. In vivo, serum levels of AGEs are elevated in patients with osteoporosis as well. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and osteoporosis. In this paper, we would like to propose the possible ways of testing our hypotheses. Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for osteoporotic bone fractures in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for osteoporotic bone fractures as well? Furthermore, are increased levels of AGEs and RAGE in bone tissues associated with high risk for bone fractures in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and osteoporosis.

Animals↗
PubMed2005

Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats.

The metabolism of 1-(3-trifluoromethylphenyl)piperazine (TFMPP), a recently banned designer drug, in rats was studied by analysing its urinary metabolites. p-Hydroxy-TFMPP (p-OH-TFMPP) was isolated and identified as the main metabolite by using nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS). The time-course excretion profiles of TFMPP and p-OH-TFMPP in rats were investigated following a single intraperitoneal dosing of 5 mg kg(-1) TFMPP by using an optimized analytical procedure that combined solid-phase extraction and LC-ESI MS techniques. The cumulative amount of p-OH-TFMPP excreted within the first 48 h reached approximately 64% of the dose, of which 70% was the glucuronide conjugated form. The cumulative amount of parent TFMPP excreted was less than 0.7% of the dose. The results suggest that p-OH-TFMPP would be the most relevant metabolite to be detected for TFMPP exposure in the forensic and clinical analysis of human urine.

Animals↗
PubMed2005

Abnormal renal structural alterations during the development of diabetes mellitus in Otsuka Long-Evans Tokushima Fatty rats.

AIM: The aim of this study was to investigate the renal structural properties in diabetic nephropathy. METHODS: Flow-pressure and pressure-glomerular filtration rate (GFR) relationships were determined for maximally vasodilated kidneys at 10 (pre-diabetic stage) and 42 weeks of age (diabetic stage) in Otsuka Long-Evans Tokushima Fatty rats (OLETF), an animal model of type 2 diabetes mellitus, using age-matched Long-Evans Tokushima Otsuka rats (LETO) as non-diabetic controls (n = 9 of each age for each strain). Kidneys were then perfusion-fixed for histological analysis. RESULTS: At 10 weeks of age, the slope of flow-pressure relationship (minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature) was steeper in OLETF than in LETO. In contrast, the threshold pressure for beginning filtration (preglomerular-to-postglomerular vascular resistance ratio) at pressure-GFR relationship did not differ between the two strains; however, the slope of the relationship (glomerular filtration capacity) was lower in OLETF than in LETO. Thus, in the kidneys of 10-week-old OLETF rats, vascular narrowing and impaired glomerular filtration capacity already existed with no abnormalities in preglomerular-to-postglomerular vascular resistance ratio. From the age of 10-42 weeks, the following results were obtained: (1) Minimal renal vascular resistance decreased in both strains, but it diminished markedly in OLETF. (2) The pressure for beginning filtration increased in LETO, but remained unchanged in OLETF. (3) Glomerular filtration capacity decreased to the similar extent in both strains. (4) Histologically, the vascular lumen and wall thickness increased in the interlobular arteries of both strains. However, vascular luminal widening was more pronounced in OLETF, resulting in the reduction in wall to lumen ratio. (5) Glomerular injuries and increased blood pressure occurred only in OLETF. CONCLUSION: In conclusion, during progression from the prediabetic to diabetic stage of OLETF, the pre-existing vascular narrowing was markedly attenuated without the concomitant increase in preglomerular-to-postglomerular vascular resistance ratio. Combined with increased blood pressure, these renal structural alterations could lead to the elevation of intraglomerular pressure in OLETF.

Animals↗
PubMed2005

Olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, protects against renal damage in advanced glycation end product (age)-injected rats.

Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the molecular mechanisms for the development and progression of diabetic nephropathy are not fully understood, the formation of advanced glycation end products (AGEs) and activation of the renin-angiotensin system (RAS) have been considered to be the main factors participating in the pathogenesis of diabetic nephropathy. However, functional cross-talk between AGEs and the RAS remains to be elucidated. In this study, we examined the effects of oral administration of olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, on renal damage in AGE-treated rats. Administration of olmesartan medoxomil significantly inhibited the increase of systolic and diastolic blood pressure levels and urinary N-acetyl-beta-D-glucosaminidase activity in exogenously AGE-injected rats. Furthermore, olmesartan medoxomil treatment also prevented glomerulosclerosis in AGE-treated rats. These results indicate that exogenous AGE treatment could induce renal damage via the activation of the RAS. Our study suggests that olmesartan medoxomil could be a valuable drug for the treatment of diabetic nephropathy by blocking the deleterious effects of AGEs.

Acetylglucosamine↗
PubMed2005

Tyrosinase induction and inactivation in normal cultured human melanocytes by endothelin-1.

Since endothelin was found to be expressed in epithelial cells as well as in vascular endothelial cells, the functional regulation of melanocytes with endothelin has been actively investigated. In particular, it has been suggested that endothelin may influence pigmentation and depigmentation, which are mediated by melanocytes. In the present study, we investigated the regulation of melanocyte function and tyrosinase expression by endothelin from the point of view of tyrosinase protein expression and enzyme activity. The influence of endothelins on melanocyte function was assessed. Melanocytes showed a dose-dependent increase in cell proliferation with the addition of endothelin-1. When the confluence of melanocytes was cultured with endothelin-1 for 72 h, tyrosinase activity in melanocytes was significantly and dose-dependently decreased. In contrast, there was no significant change with endothelin-3. However, tyrosinase protein expression of melanocytes was significantly and dose-dependently increased by endothelin-1, but endothelin-3 had no effect. Both the suppression of enzyme activity and the enhanced protein expression were regulated by the ETA receptor antagonist, BQ123. In view of these observations, we conclude that endothelin-1-induced tyrosinase is mediated by ETA receptors. However, the reason for the decrease in the specific activity of tyrosinase remains unknown, and our results suggest that another mechanism underlying the activation of tyrosinase is present in addition to the inductive action of endothelin-1 on tyrosinase.

Cell Proliferation↗