7 results on '"Ulucan C"'
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2. Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress.
- Author
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Okumura S, Vatner DE, Kurotani R, Bai Y, Gao S, Yuan Z, Iwatsubo K, Ulucan C, Kawabe J, Ghosh K, Vatner SF, Ishikawa Y, Okumura, Satoshi, Vatner, Dorothy E, Kurotani, Reiko, Bai, Yunzhe, Gao, Shumin, Yuan, Zengrong, Iwatsubo, Kousaku, and Ulucan, Coskun
- Published
- 2007
- Full Text
- View/download PDF
3. Pseudonormalization: clinical, electrocardiographic, echocardiographic, and angiographic characteristics.
- Author
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Ulucan C, Yavuzgil O, Kayikcioglu M, Can L, Payzin S, Kultursay H, Soydan I, Hasdemir C, Ulucan, Cem, Yavuzgil, Oğuz, Kayikçioğlu, Meral, Can, Levent, Payzin, Serdar, Kültürsay, Hakan, Soydan, Inan, and Hasdemir, Can
- Abstract
Objective: Spontaneous pseudonormalization (PN) is a unique 12-lead electrocardiography (ECG) finding which has been reported to be associated with severe, transmural myocardial ischemia. To date, a paucity of data exists about the incidence and clinical characteristics of patients with PN. Therefore the aim of this study was to investigate the incidence and the electrocardiographic, echocardiographic, and angiographic characteristics of patients with PN.Methods: Clinical, laboratory, electrocardiographic, echocardiographic, and angiographic characteristics of 12 consecutive patients with PN on 12-lead ECG (Group 1) were compared with patients (Group 2, n=28) presenting with acute coronary syndrome (ACS) associated with ST-T wave changes without PN.Results: All patients presented with chest pain. The incidence of PN among patients presenting with ACS was 1%. Pseudonormalization was present in precordial leads in 11 and in inferior leads in 1 patient. Nine out of 12 (75%) patients in Group 1, 16 out of 28 (57%) patients in Group 2 had elevation of cardiac enzymes compatible with acute myocardial infarction. Severely narrowed or totally occluded ischemia and/or infarction-related coronary arteries were present in all patients in Group 1, in 20 (71%) patients in Group 2. Three patients in Group I and one patient in Group 2 had coronary artery thrombus formation. Group 1 patients had worse coronary collateral grading in comparison to Group 2 patients.Conclusion: Pseudonormalization is a rare entity and it is typically associated with severely narrowed or totally occluded coronary arteries along with thrombus formation, and poor coronary collateral development. [ABSTRACT FROM AUTHOR]- Published
- 2007
4. Epac increases melanoma cell migration by a heparan sulfate-related mechanism.
- Author
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Baljinnyam E, Iwatsubo K, Kurotani R, Wang X, Ulucan C, Iwatsubo M, Lagunoff D, and Ishikawa Y
- Subjects
- Animals, Cell Line, Tumor, Guanine Nucleotide Exchange Factors genetics, Humans, Melanoma pathology, Melanoma, Experimental metabolism, Melanoma, Experimental pathology, Mice, Mice, Nude, Neoplasm Invasiveness, Neoplasm Transplantation, Phosphatidylinositol 3-Kinases physiology, Protein Transport, Signal Transduction, Tubulin metabolism, Cell Movement physiology, Guanine Nucleotide Exchange Factors physiology, Heparitin Sulfate biosynthesis, Melanoma metabolism, Sulfotransferases metabolism, Syndecan-2 metabolism
- Abstract
Melanoma, the most malignant form of human skin cancer, has a poor prognosis due to its strong metastatic ability. It was recently demonstrated that Epac, an effector molecule of cAMP, is involved in regulating cell migration; however, the role of Epac in melanoma cell migration remains unclear. We thus examined whether Epac regulates cell migration and metastasis of melanoma. Epac activation, by either specific agonist or overexpression of Epac, increased melanoma cell migration. Deletion of endogenous Epac with small interfering RNA decreased basal melanoma cell migration. These data suggested a major role of Epac in melanoma cell migration. Epac-induced cell migration was mediated by translocation of syndecan-2, a cell-surface heparan sulfate proteoglycan, to lipid rafts. This syndecan-2 translocation was regulated by tubulin polymerization via the Epac/phosphoinositol-3 kinase pathway. Epac-induced cell migration was also regulated by the production of heparan sulfate, a major extracellular matrix. Epac-induced heparan sulfate production was attributable to the increased expression of N-deacetylase/N-sulfotransferase-1 (NDST-1) accompanied by an increased NDST-1 translation rate. Finally, Epac overexpression enhanced lung colonization of melanoma cells in mice. Taken together, these data indicate that Epac regulates melanoma cell migration/metastasis mostly via syndecan-2 translocation and heparan sulfate production.
- Published
- 2009
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5. Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration.
- Author
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Yokoyama U, Minamisawa S, Quan H, Akaike T, Jin M, Otsu K, Ulucan C, Wang X, Baljinnyam E, Takaoka M, Sata M, and Ishikawa Y
- Subjects
- Animals, Aorta embryology, Aorta growth & development, Aorta metabolism, Cell Shape, Cells, Cultured, Cyclic AMP analogs & derivatives, Cyclic AMP pharmacology, Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors, Cyclic AMP-Dependent Protein Kinases metabolism, Disease Models, Animal, Female, Femoral Artery injuries, Femoral Artery metabolism, Femoral Artery pathology, Gestational Age, Guanine Nucleotide Exchange Factors antagonists & inhibitors, Guanine Nucleotide Exchange Factors genetics, Male, Mice, Mice, Inbred ICR, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular embryology, Muscle, Smooth, Vascular growth & development, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle enzymology, Pregnancy, Protein Kinase Inhibitors pharmacology, Rats, Rats, Wistar, Thionucleotides pharmacology, Time Factors, Transduction, Genetic, Tunica Intima drug effects, Tunica Intima embryology, Tunica Intima growth & development, Up-Regulation, Cell Movement drug effects, Guanine Nucleotide Exchange Factors metabolism, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle metabolism, Signal Transduction drug effects, Tunica Intima metabolism
- Abstract
Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA. We thus examined whether Epac plays a distinct role from PKA in vascular remodeling. To examine the role of Epac and PKA in migration, we used primary culture smooth muscle cells from both the fetal and adult rat aorta. A cAMP analog selective to PKA, 8-(4-parachlorophenylthio)-cAMP (pCPT-cAMP), decreased cell migration, whereas an Epac-selective analog, 8-pCPT-2'-O-Me-cAMP, enhanced migration. Adenovirus-mediated gene transfer of PKA decreased cell migration, whereas that of Epac1 significantly enhanced cell migration. Striking morphological differences were observed between pCPT-cAMP- and 8-pCPT-2'-O-Me-cAMP-treated aortic smooth muscle cells. Furthermore, overexpression of Epac1 enhanced the development of neointimal formation in fetal rat aortic tissues in organ culture. When the mouse femoral artery was injured mechanically in vivo, we found that the expression of Epac1 was upregulated in vascular smooth muscle cells, whereas that of PKA was downregulated with the progress of neointimal thickening. Our findings suggest that Epac1, in opposition to PKA, increases vascular smooth muscle cell migration. Epac may thus play an important role in advancing vascular remodeling and restenosis upon vascular injury.
- Published
- 2008
- Full Text
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6. Head-to-head comparison of BNP and IL-6 as markers of clinical and experimental heart failure: Superiority of BNP.
- Author
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Birner CM, Ulucan C, Fredersdorf S, Rihm M, Löwel H, Stritzke J, Schunkert H, Hengstenberg C, Holmer S, Riegger G, and Luchner A
- Subjects
- Animals, Biomarkers blood, Chronic Disease, Disease Models, Animal, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction blood, RNA, Messenger blood, Rabbits, Species Specificity, Ventricular Dysfunction, Left blood, Heart Failure blood, Interleukin-6 blood, Natriuretic Peptide, Brain blood, Nerve Tissue Proteins blood, Protein Precursors blood
- Abstract
Activation of BNP and IL-6 are hallmarks of left ventricular (LV) dysfunction and congestive heart failure (CHF). To assess the relative activation of BNP and IL-6 in clinical and experimental heart failure, we performed a human study in which plasma N-terminal proBNP (NT-proBNP) and IL-6 were measured in a large group of patients in the chronic phase after myocardial infarction (MI) and an animal study in which LV gene expression of BNP and IL-6 was assessed in rapid ventricular pacing-induced heart failure. In the human study, NT-proBNP and IL-6 were measured by non-extracted, enzyme-linked immunoassay in 845 subjects (n=468 outpatients after MI, MONICA MI register Augsburg; and 377 siblings without MI, control). NT-proBNP (295+/-23pg/mL vs. CTRL 84+/-8, P<0.05) and IL-6 (2.7+/-0.1pg/mL vs. CTRL 2.1+/-0.1, P<0.05) were both elevated in subjects with MI. These increases were particularly pronounced in the presence of concomitant CHF (both P<0.01 vs. CTRL) and LV dysfunction (EF<45%, both P<0.05 vs. CTRL). However, NT-proBNP was significantly correlated with several cardiac structural and functional parameters (EF, LVMI, history of MI, CHF symptoms; all P<0.05) upon regression analysis whereas IL-6 was only correlated with history of MI (P<0.001). Accordingly, MI subjects with symptomatic LV dysfunction were detected by NT-proBNP with a greater sensitivity, specificity, and ROC-area (85%, 88%, and 0.87, respectively) as compared to IL-6 (69%, 53%, and 0.67, respectively). In the animal study, IL-6 and BNP expression were both significantly elevated in CHF (both P<0.05) but with a much greater absolute activation of BNP. In addition, BNP mRNA expression displayed a stronger inverse correlation with LV function (r=-0.74; P<0.001) than IL-6 (r=-0.53; P=0.001) and was a markedly more sensitive and specific molecular marker of LV dysfunction (sensitivity 91%, specificity 100%, ROC-area 0.94) than IL-6 (sensitivity 74%, specificity 83%, ROC-area 0.87). Our animal study provides evidence that IL-6 expression is activated in heart failure but to a significantly lesser degree than that of BNP. Both the stronger expression of BNP and the better correlation with LV function provide the molecular basis for a diagnostic superiority of NT-proBNP in clinical LV dysfunction and heart failure.
- Published
- 2007
- Full Text
- View/download PDF
7. Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.
- Author
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Ulucan C, Wang X, Baljinnyam E, Bai Y, Okumura S, Sato M, Minamisawa S, Hirotani S, and Ishikawa Y
- Subjects
- Adenylyl Cyclases genetics, Adenylyl Cyclases metabolism, Animals, COS Cells, Cardiotonic Agents, Carrier Proteins metabolism, Cell Line, Cell Line, Tumor, Chlorocebus aethiops, Cyclic AMP-Dependent Protein Kinase Catalytic Subunits, Cyclic AMP-Dependent Protein Kinases genetics, Cyclic AMP-Dependent Protein Kinases metabolism, GTP-Binding Protein alpha Subunits, Gs genetics, GTP-Binding Protein alpha Subunits, Gs metabolism, Gene Expression Regulation, Developmental, Guanine Nucleotide Exchange Factors genetics, Heart growth & development, Humans, Hypertrophy, Isoenzymes genetics, Isoenzymes metabolism, Isoproterenol, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Signal Transduction physiology, rap1 GTP-Binding Proteins genetics, rap1 GTP-Binding Proteins metabolism, Guanine Nucleotide Exchange Factors metabolism, Heart embryology, Myocardium metabolism, Myocardium pathology
- Abstract
Although it has been shown that Epac1 mRNA is expressed ubiquitously and Epac2 mRNA predominantly in the brain and endocrine tissues, developmental and pathophysiological changes of these molecules have not been characterized. Developmental changes were analyzed in murine heart, brain, kidneys, and lungs by RT-PCR analysis, which revealed more drastic developmental changes of Epac2 mRNA than Epac1. Only the Epac2 mRNA in kidney showed a transient expression pattern with dramatic decline into adulthood. In addition to developmental changes, we found that Epac gene expression was upregulated in myocardial hypertrophy induced by chronic isoproterenol infusion or pressure overload by transverse aortic banding. Both Epac1 and Epac2 mRNA were upregulated in isoproterenol-induced left ventricular hypertrophy, whereas only Epac1 was increased in pressure overload-induced hypertrophy. Stimulation of H9c2, cardiac myoblast cells, with fetal calf serum, which can induce myocyte hypertrophy, upregulated Epac1 protein expression. We also demonstrated that Epac was the limiting moiety, relative to Rap, in the Epac-Rap signaling pathway in terms of stoichiometry and that Epac stimulation led to the activation of ERK1/2. Our data suggest the functional involvement of Epac in organogenesis and also in physiological as well as pathophysiological processes, such as cardiac hypertrophy. Furthermore, our results suggest the importance of the stoichiometry of Epac over that of Rap in cellular biological effects.
- Published
- 2007
- Full Text
- View/download PDF
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