Joong-yeol Park - Academia.edu (original) (raw)
Papers by Joong-yeol Park
Atherosclerosis, Jan 25, 2015
Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with corona... more Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with coronary artery calcification (CAC). CAC progression is an important marker of atherosclerosis and correlates with future cardiovascular risk. However, there is a lack of research that directly examines the association between serum GGT and CAC progression. The aim of this study was to elucidate the association between serum GGT activity and CAC progression. We enrolled 1246 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. To eliminate the dependence of the inter scan variability on the baseline CAC scores, square root-transformed CAC scores were used to analyze CAC progression. In addition, the annualized rate of change in CAC scores was computed. Serum GGT activities were significantly higher in "progressors" than "nonprogressors". The prevalence of progression increased with the GGT tertile (11.9%, 20.1% and 27.9%...
PloS one, 2015
The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asia... more The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asian population remains controversial. In this study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines is better aligned with the presence of subclinical coronary atherosclerosis detected by CCTA (coronary computed tomography angiography) compared to the previously recommended 2004 NCEP ATP III guidelines. We collected the data from 5,837 asymptomatic subjects who underwent CCTA using MDCT during routine health examinations. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy according to the 2013 ACC/AHA and 2004 NCEP ATP III guidelines. We defined the presence and severity of subclinical coronary atherosclerosis detected in CCTA according to the presence of significant coronary artery stenosis (defined as >50% stenosis), plaques, and the degree of coronary calcification. As compared...
Journal of diabetes, Jan 10, 2015
To compare the association between cardiovascular diseases (CVD) and prediabetes defined by fasti... more To compare the association between cardiovascular diseases (CVD) and prediabetes defined by fasting plasma glucose (FPG)-only, HbA1c-only, or combined criteria in a Korean population. In total, 76,434 South Korean individuals who voluntarily underwent a general health examination in the Health Screening and Promotion Center at Asan Medical Center were analyzed after excluding patients with previous history of CVD. CVD events and death during a median follow-up of 3.1 (interquartile range, 1.9-4.3) years were recognized from the nationwide health insurance claims database and death certificates by using ICD-10 codes. Age- and sex-adjusted hazard ratios (HRs) for overall CVD events were significantly increased for participants with prediabetes by FPG-only criteria (1.19 [1.08-1.31]), HbA1c-only criteria (1.28 [1.16-1.42]), and combined criteria (1.20 [1.09-1.32]). After adjusting for multiple conventional risk factors such as hypertension, LDL and HDL cholesterol levels, smoking statu...
The Journal of Korean Diabetes Association, 2007
성균관대학교 의과대학 내과학교실, 건국대학교 의과대학 내과학교실1, 인제대학교 의과대학 내과학교실2, 울산대학교 의과대학 내과학교실3, 예방의학교실4 원종철, 박중열3, 송기... more 성균관대학교 의과대학 내과학교실, 건국대학교 의과대학 내과학교실1, 인제대학교 의과대학 내과학교실2, 울산대학교 의과대학 내과학교실3, 예방의학교실4 원종철, 박중열3, 송기호1, 이우제2, 고은희3, 남궁일성3, 한성민3, 이무송4, 김민선3, 이기업3
Diabetes & metabolism journal, 2015
Oxidative stress is known to be associated with progression of diabetic kidney disease. Cerulopla... more Oxidative stress is known to be associated with progression of diabetic kidney disease. Ceruloplasmin acts as a pro-oxidant under conditions of severe oxidative stress. Thus, we conducted a longitudinal observational study to evaluate whether the serum ceruloplasmin level is a predictive biomarker for progression of diabetic nephropathy. A total of 643 Korean men with type 2 diabetes mellitus were enrolled. Serum ceruloplasmin was measured using a nephelometric method. Progression of diabetic nephropathy was defined as transition in albuminuria class (i.e., normoalbuminuria to microalbuminuria, microalbuminuria to macroalbuminuria, or normoalbuminuria to macroalbuminuria) and/or a greater than 2-fold increase of serum creatinine at follow-up compared with the baseline value. During the follow-up period (median, 2.7 years; range, 0.3 to 4.4 years), 49 of 643 patients (7.6%) showed the progression of diabetic nephropathy and three patients (0.5%) developed end-stage renal disease. Bas...
Kidney international, Jan 24, 2015
Obesity has become an important risk factor for chronic kidney disease (CKD). The metabolically h... more Obesity has become an important risk factor for chronic kidney disease (CKD). The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. However, its prognostic value remains controversial and may depend on the health outcome being investigated. To assess this, we examined the risk of MHO phenotype with incident CKD in a Korean population of 41,194 people without CKD. Individuals were stratified by body mass index (cutoff value, 25.0 kg/m(2)) and metabolic health state (assessed using Adult Treatment Panel-III criteria). Incident CKD was defined as a glomerular filtration rate of <60 ml/min per 1.73 m(2) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Over the median follow-up period of 38.7 months, 356 of the individuals developed incident CKD. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident CKD with a multivariate-adjusted hazard r...
The American journal of cardiology, Jan 8, 2015
There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atheros... more There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atherosclerosis. Therefore, we sought to investigate the impact of DM on the risk of subclinical atherosclerosis in asymptomatic subjects. We analyzed 2,034 propensity score-matched asymptomatic subjects who underwent coronary computed tomographic angiography (mean age 55.9 ± 8.2 years; men 1,725 [84.8%]). Coronary artery calcium score, degree and extent of coronary artery disease (CAD), and clinical outcomes were assessed. High-risk CAD was defined as at least 2-vessel coronary disease with proximal left anterior descending artery involvement, 3-vessel disease, or left main disease. Compared with subjects without DM, those matched with DM had higher coronary artery calcium score (89.9 ± 240.4 vs 62.8 ± 179.5, p = 0.004) and more significant CAD (≥50% diameter stenosis, 15.2% vs 10.2%, p = 0.001), largely in the form of 1-vessel disease (10.8% vs 7.3%, p = 0.007). However, there were no signifi...
Diabetes & Metabolism Journal, 2015
Cardiovascular Diabetology, 2015
Hypertension, 2005
Neointimal formation, the leading cause of restenosis, is caused by proliferation of vascular smo... more Neointimal formation, the leading cause of restenosis, is caused by proliferation of vascular smooth muscle cells (VSMCs). Patients with diabetes mellitus have higher restenosis rates after coronary angioplasty than nondiabetic patients. Cilostazol, a selective type 3 phosphodiesterase inhibitor, is currently used to treat patients with diabetic vascular complications. Cilostazol is a potent antiplatelet agent that inhibits VSMC proliferation. In the present study, we examine whether the antiproliferative effect of cilostazol on VSMCs is mediated by inhibition of an important cell cycle transcription factor, E2F. Cilostazol inhibited the proliferation of human VSMCs in response to high glucose in vitro and virtually abolished neointimal formation in rats subjected to carotid artery injury in vivo. Moreover, the compound suppressed high-glucose-induced E2F-DNA binding activity, and the expression of E2F1, E2F2, cyclin A, and PCNA proteins. These data suggest that the beneficial effec...
Diabetes & Metabolism Journal, 2014
Korean Diabetes Journal, 2009
ABSTRACT Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation... more ABSTRACT Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation of insulin sensitivity in skeletal muscle. Recent studies also suggested NO as an important molecule regulating mitochondrial biogenesis. This study examined the effect of the NO donor, 3-morpholinosydnonimine (SIN-1), on glucose metabolism in skeletal muscle and tested the hypothesis that NO's effect on glucose metabolism is mediated by its effect on mitochondrial function.
Biochemical and biophysical research communications, Jan 13, 2015
Proteostasis regulation using naturally occurring small molecules has been considered as a promis... more Proteostasis regulation using naturally occurring small molecules has been considered as a promising strategy for manipulating cancer sensitivity and therapy. Here, we identify a small molecule Hsp90 inhibitor radicicol that induces intracellular accumulation of cytotoxic clusterin variant. In the mechanistic basis, this variant proved to be a product disposed from the stressed ER. During this process, inhibitory effect of radicicol on protein degradation results in cytosolic accumulation of glycan-deficient clusterin variant that signals cell death. These results provide a therapeutic insight into the targeted proteostasis perturbation of clusterin as an anti-cancer strategy.
Journal of diabetes investigation, Jan 4, 2014
Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have e... more Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA-IR) and colorectal adenoma. We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non-specific colitis, non-adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting seru...
Nature Neuroscience, 2006
Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest th... more Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest that the forkhead transcription factor Foxo1 is an important mediator of insulin signaling in peripheral tissues. Here we demonstrate that in normal mice, hypothalamic Foxo1 expression is reduced by the anorexigenic hormones insulin and leptin. These hormones&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; effects on feeding are inhibited when hypothalamic Foxo1 is activated, establishing a new signaling pathway through which insulin and leptin regulate food intake in hypothalamic neurons. Moreover, activation of Foxo1 in the hypothalamus increases food intake and body weight, whereas inhibition of Foxo1 decreases both. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, but suppresses the transcription of anorexigenic proopiomelanocortin by antagonizing the activity of signal transducer-activated transcript-3 (STAT3). Our data suggest that hypothalamic Foxo1 is an important regulator of food intake and energy balance.
Korean Diabetes Journal, 2010
Mitochondria play key roles in energy production and intracellular reactive oxygen species (ROS) ... more Mitochondria play key roles in energy production and intracellular reactive oxygen species (ROS) generation. Lines of evidence have shown that mitochondrial dysfunction contributes to the development of metabolic syndrome. The causes of mitochondrial dysfunction are complex, but overnutrition and sedentary living are among the best known causes of mitochondrial dysfunction. ATP synthesized in the mitochondria is exchanged for cytosolic ADP by adenine nucleotide translocator (ANT) to provide a continuous supply of ADP to mitochondria. We recently found that ANT function is essential for peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s action on endothelial cells. PGC-1alpha is a transcriptional coactivator of nuclear receptors, playing an important role in fatty acid oxidation and mitochondrial biogenesis. Recent studies have shown that PGC-1alpha decreases intracellular ROS generation by increasing the expression of antioxidant genes. In our study, PGC-1alpha reduced cell apoptosis and ROS generation in endothelial cells by increasing ATP/ADP translocase activity of ANT and ANT1 expression. Here we review the role of ANT in maintaining proper mitochondrial function, and possible role of ANT dysfunction in the pathogenesis of metabolic syndrome.
Korean Diabetes Journal, 2010
Korean Diabetes Journal, 2010
FEBS Letters, 2014
OB-Rb is a crucial factor for leptin signaling. This study was initially motivated by the observa... more OB-Rb is a crucial factor for leptin signaling. This study was initially motivated by the observation that OB-Rb expression is constitutively inhibited in the early secretory pathway. Our analyses reveal that OB-Rb contains a less hydrophobic, but functionally active N-terminal signal sequence. Constitutive translocational attenuation attributable to a less efficient signal sequence proved to be a reason for low protein level of OB-Rb. By contrast, enhanced signal sequence efficiency rescues translocation and cell surface expression of OB-Rb, and eventually potentiates leptin signaling. These observations provide considerable insight into the therapeutic enhancement of OB-Rb translocation as a potential strategy for leptin resistance.
The International Journal of Biochemistry & Cell Biology, 2005
Atherosclerosis, Jan 25, 2015
Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with corona... more Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with coronary artery calcification (CAC). CAC progression is an important marker of atherosclerosis and correlates with future cardiovascular risk. However, there is a lack of research that directly examines the association between serum GGT and CAC progression. The aim of this study was to elucidate the association between serum GGT activity and CAC progression. We enrolled 1246 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. To eliminate the dependence of the inter scan variability on the baseline CAC scores, square root-transformed CAC scores were used to analyze CAC progression. In addition, the annualized rate of change in CAC scores was computed. Serum GGT activities were significantly higher in "progressors" than "nonprogressors". The prevalence of progression increased with the GGT tertile (11.9%, 20.1% and 27.9%...
PloS one, 2015
The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asia... more The usefulness of the 2013 ACC/AHA guidelines for the management of blood cholesterol in the Asian population remains controversial. In this study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines is better aligned with the presence of subclinical coronary atherosclerosis detected by CCTA (coronary computed tomography angiography) compared to the previously recommended 2004 NCEP ATP III guidelines. We collected the data from 5,837 asymptomatic subjects who underwent CCTA using MDCT during routine health examinations. Based on risk factor assessment and lipid data, we determined guideline-based eligibility for statin therapy according to the 2013 ACC/AHA and 2004 NCEP ATP III guidelines. We defined the presence and severity of subclinical coronary atherosclerosis detected in CCTA according to the presence of significant coronary artery stenosis (defined as >50% stenosis), plaques, and the degree of coronary calcification. As compared...
Journal of diabetes, Jan 10, 2015
To compare the association between cardiovascular diseases (CVD) and prediabetes defined by fasti... more To compare the association between cardiovascular diseases (CVD) and prediabetes defined by fasting plasma glucose (FPG)-only, HbA1c-only, or combined criteria in a Korean population. In total, 76,434 South Korean individuals who voluntarily underwent a general health examination in the Health Screening and Promotion Center at Asan Medical Center were analyzed after excluding patients with previous history of CVD. CVD events and death during a median follow-up of 3.1 (interquartile range, 1.9-4.3) years were recognized from the nationwide health insurance claims database and death certificates by using ICD-10 codes. Age- and sex-adjusted hazard ratios (HRs) for overall CVD events were significantly increased for participants with prediabetes by FPG-only criteria (1.19 [1.08-1.31]), HbA1c-only criteria (1.28 [1.16-1.42]), and combined criteria (1.20 [1.09-1.32]). After adjusting for multiple conventional risk factors such as hypertension, LDL and HDL cholesterol levels, smoking statu...
The Journal of Korean Diabetes Association, 2007
성균관대학교 의과대학 내과학교실, 건국대학교 의과대학 내과학교실1, 인제대학교 의과대학 내과학교실2, 울산대학교 의과대학 내과학교실3, 예방의학교실4 원종철, 박중열3, 송기... more 성균관대학교 의과대학 내과학교실, 건국대학교 의과대학 내과학교실1, 인제대학교 의과대학 내과학교실2, 울산대학교 의과대학 내과학교실3, 예방의학교실4 원종철, 박중열3, 송기호1, 이우제2, 고은희3, 남궁일성3, 한성민3, 이무송4, 김민선3, 이기업3
Diabetes & metabolism journal, 2015
Oxidative stress is known to be associated with progression of diabetic kidney disease. Cerulopla... more Oxidative stress is known to be associated with progression of diabetic kidney disease. Ceruloplasmin acts as a pro-oxidant under conditions of severe oxidative stress. Thus, we conducted a longitudinal observational study to evaluate whether the serum ceruloplasmin level is a predictive biomarker for progression of diabetic nephropathy. A total of 643 Korean men with type 2 diabetes mellitus were enrolled. Serum ceruloplasmin was measured using a nephelometric method. Progression of diabetic nephropathy was defined as transition in albuminuria class (i.e., normoalbuminuria to microalbuminuria, microalbuminuria to macroalbuminuria, or normoalbuminuria to macroalbuminuria) and/or a greater than 2-fold increase of serum creatinine at follow-up compared with the baseline value. During the follow-up period (median, 2.7 years; range, 0.3 to 4.4 years), 49 of 643 patients (7.6%) showed the progression of diabetic nephropathy and three patients (0.5%) developed end-stage renal disease. Bas...
Kidney international, Jan 24, 2015
Obesity has become an important risk factor for chronic kidney disease (CKD). The metabolically h... more Obesity has become an important risk factor for chronic kidney disease (CKD). The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. However, its prognostic value remains controversial and may depend on the health outcome being investigated. To assess this, we examined the risk of MHO phenotype with incident CKD in a Korean population of 41,194 people without CKD. Individuals were stratified by body mass index (cutoff value, 25.0 kg/m(2)) and metabolic health state (assessed using Adult Treatment Panel-III criteria). Incident CKD was defined as a glomerular filtration rate of <60 ml/min per 1.73 m(2) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Over the median follow-up period of 38.7 months, 356 of the individuals developed incident CKD. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident CKD with a multivariate-adjusted hazard r...
The American journal of cardiology, Jan 8, 2015
There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atheros... more There are limited data on the impact of diabetes mellitus (DM) on the risk of subclinical atherosclerosis. Therefore, we sought to investigate the impact of DM on the risk of subclinical atherosclerosis in asymptomatic subjects. We analyzed 2,034 propensity score-matched asymptomatic subjects who underwent coronary computed tomographic angiography (mean age 55.9 ± 8.2 years; men 1,725 [84.8%]). Coronary artery calcium score, degree and extent of coronary artery disease (CAD), and clinical outcomes were assessed. High-risk CAD was defined as at least 2-vessel coronary disease with proximal left anterior descending artery involvement, 3-vessel disease, or left main disease. Compared with subjects without DM, those matched with DM had higher coronary artery calcium score (89.9 ± 240.4 vs 62.8 ± 179.5, p = 0.004) and more significant CAD (≥50% diameter stenosis, 15.2% vs 10.2%, p = 0.001), largely in the form of 1-vessel disease (10.8% vs 7.3%, p = 0.007). However, there were no signifi...
Diabetes & Metabolism Journal, 2015
Cardiovascular Diabetology, 2015
Hypertension, 2005
Neointimal formation, the leading cause of restenosis, is caused by proliferation of vascular smo... more Neointimal formation, the leading cause of restenosis, is caused by proliferation of vascular smooth muscle cells (VSMCs). Patients with diabetes mellitus have higher restenosis rates after coronary angioplasty than nondiabetic patients. Cilostazol, a selective type 3 phosphodiesterase inhibitor, is currently used to treat patients with diabetic vascular complications. Cilostazol is a potent antiplatelet agent that inhibits VSMC proliferation. In the present study, we examine whether the antiproliferative effect of cilostazol on VSMCs is mediated by inhibition of an important cell cycle transcription factor, E2F. Cilostazol inhibited the proliferation of human VSMCs in response to high glucose in vitro and virtually abolished neointimal formation in rats subjected to carotid artery injury in vivo. Moreover, the compound suppressed high-glucose-induced E2F-DNA binding activity, and the expression of E2F1, E2F2, cyclin A, and PCNA proteins. These data suggest that the beneficial effec...
Diabetes & Metabolism Journal, 2014
Korean Diabetes Journal, 2009
ABSTRACT Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation... more ABSTRACT Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation of insulin sensitivity in skeletal muscle. Recent studies also suggested NO as an important molecule regulating mitochondrial biogenesis. This study examined the effect of the NO donor, 3-morpholinosydnonimine (SIN-1), on glucose metabolism in skeletal muscle and tested the hypothesis that NO's effect on glucose metabolism is mediated by its effect on mitochondrial function.
Biochemical and biophysical research communications, Jan 13, 2015
Proteostasis regulation using naturally occurring small molecules has been considered as a promis... more Proteostasis regulation using naturally occurring small molecules has been considered as a promising strategy for manipulating cancer sensitivity and therapy. Here, we identify a small molecule Hsp90 inhibitor radicicol that induces intracellular accumulation of cytotoxic clusterin variant. In the mechanistic basis, this variant proved to be a product disposed from the stressed ER. During this process, inhibitory effect of radicicol on protein degradation results in cytosolic accumulation of glycan-deficient clusterin variant that signals cell death. These results provide a therapeutic insight into the targeted proteostasis perturbation of clusterin as an anti-cancer strategy.
Journal of diabetes investigation, Jan 4, 2014
Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have e... more Insulin has been associated with the risk of colorectal cancer (CRC). However, few studies have evaluated the association between insulin and colorectal adenoma. We investigated the relationship between fasting serum insulin levels or homeostasis model assessment of insulin resistance (HOMA-IR) and colorectal adenoma. We retrospectively enrolled 15,427 participants who underwent both fasting serum insulin measurement and colonoscopy for a routine health examination at Asan Medical Center from January 2007 to December 2008. Participants with a history of any cancer, previous colectomy or polypectomy, those taking antidiabetic medications, and inflammatory bowel disease, non-specific colitis, non-adenomatous polyps only or CRC on colonoscopic findings were excluded. Finally, 3,606 participants with histologically confirmed colorectal adenoma and 6,019 controls with no abnormal findings on colonoscopy were included. Participants were categorized into quartiles (Q) based on fasting seru...
Nature Neuroscience, 2006
Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest th... more Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest that the forkhead transcription factor Foxo1 is an important mediator of insulin signaling in peripheral tissues. Here we demonstrate that in normal mice, hypothalamic Foxo1 expression is reduced by the anorexigenic hormones insulin and leptin. These hormones&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; effects on feeding are inhibited when hypothalamic Foxo1 is activated, establishing a new signaling pathway through which insulin and leptin regulate food intake in hypothalamic neurons. Moreover, activation of Foxo1 in the hypothalamus increases food intake and body weight, whereas inhibition of Foxo1 decreases both. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, but suppresses the transcription of anorexigenic proopiomelanocortin by antagonizing the activity of signal transducer-activated transcript-3 (STAT3). Our data suggest that hypothalamic Foxo1 is an important regulator of food intake and energy balance.
Korean Diabetes Journal, 2010
Mitochondria play key roles in energy production and intracellular reactive oxygen species (ROS) ... more Mitochondria play key roles in energy production and intracellular reactive oxygen species (ROS) generation. Lines of evidence have shown that mitochondrial dysfunction contributes to the development of metabolic syndrome. The causes of mitochondrial dysfunction are complex, but overnutrition and sedentary living are among the best known causes of mitochondrial dysfunction. ATP synthesized in the mitochondria is exchanged for cytosolic ADP by adenine nucleotide translocator (ANT) to provide a continuous supply of ADP to mitochondria. We recently found that ANT function is essential for peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1alpha)&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s action on endothelial cells. PGC-1alpha is a transcriptional coactivator of nuclear receptors, playing an important role in fatty acid oxidation and mitochondrial biogenesis. Recent studies have shown that PGC-1alpha decreases intracellular ROS generation by increasing the expression of antioxidant genes. In our study, PGC-1alpha reduced cell apoptosis and ROS generation in endothelial cells by increasing ATP/ADP translocase activity of ANT and ANT1 expression. Here we review the role of ANT in maintaining proper mitochondrial function, and possible role of ANT dysfunction in the pathogenesis of metabolic syndrome.
Korean Diabetes Journal, 2010
Korean Diabetes Journal, 2010
FEBS Letters, 2014
OB-Rb is a crucial factor for leptin signaling. This study was initially motivated by the observa... more OB-Rb is a crucial factor for leptin signaling. This study was initially motivated by the observation that OB-Rb expression is constitutively inhibited in the early secretory pathway. Our analyses reveal that OB-Rb contains a less hydrophobic, but functionally active N-terminal signal sequence. Constitutive translocational attenuation attributable to a less efficient signal sequence proved to be a reason for low protein level of OB-Rb. By contrast, enhanced signal sequence efficiency rescues translocation and cell surface expression of OB-Rb, and eventually potentiates leptin signaling. These observations provide considerable insight into the therapeutic enhancement of OB-Rb translocation as a potential strategy for leptin resistance.
The International Journal of Biochemistry & Cell Biology, 2005