Comparative Analysis of Phospholipase D2 Localization in the Pancreatic Islet of Rat and Guinea Pig

Ryu, Gyeong-Ryul,Kim, Myung-Jun,Song, Chan-Hee,Min, Do-Sik,Rhie, Duck-Joo,Yoon, Shin-Hee,Hahn, Sang-June,Kim, Myung-Suk,Jo, Yang-Hyeok The Korean Society of Pharmacology 2003 The Korean Journal of Physiology & Pharmacology Vol.7 No.4

To examine the localization pattern of phospholipase D2 (PLD2) in the pancreatic islet (the islet of Langerhans) depending on species, we conducted a morphological experiment in the rat and guinea pig. Since individual islets display a typical topography with a central core of B cell mass and a peripheral boundary of A, D, and PP cells, double immunofluorescent staining with a panel of antibodies was performed to identify PLD2-immunoreactive cells in the islets PLD2 immunoreactivity was mainly present in A and PP cells of the rat pancreatic islets. And yet, in the guinea pig, PLD2 immunoreactivity was exclusively localized in A cells, and not in PP cells. These findings suggest a possibility that PLD2 is mainly located in A cells of rodent pancreatic islets, and that the existence of PLD2 in PP cells is not universal in all species. Based on these results, it is suggested that PLD2 may play a significant role in the function of A and/or PP cells via a PLD-mediated signaling pathway.

Carrier frequency of SLC26A4 mutations causing inherited deafness in the Korean population

Hyo gyeong Kim,Hwan Sub Lim,Jae Song Ryu,Hyun Chul Kim,Sang hoo Lee,Yun Tae Kim,Young Jin Kim,Kyoung Ryul Lee,Hong Joon Park,Sung Hee Han 대한의학유전학회 2014 대한의학유전학회지 Vol.11 No.2

Purpose: The mutation of the SLC26A4 gene is the second most common cause of congenital hearing loss after GJB2 mutations. It has been identified as a major cause of autosomal recessive nonsyndromic hearing loss associated with enlarged vestibular aqueduct and Pendred syndrome. Although most studies of SLC26A4 mutations have dealt with hearing-impaired patients, there are a few reports on the frequency of these mutations in the general population. The purpose of this study was to evaluate the prevalence of SLC26A4 mutations that cause inherited deafness in the general Korean population. Materials and Methods: We obtained blood samples from 144 Korean individuals with normal hearing. The samples were subjected to polymerase chain reaction to amplify the entire coding region of the SLC26A4 gene, followed by direct DNA sequencing. Results: Sequencing analysis of this gene identified 5 different variants (c.147C>G, c.225G>C, c.1723A>G, c.2168A>G, and c.2283A>G). The pathogenic mutation c.2168A>G (p.H723R) was identified in 1.39% (2/144) of the subjects with normal hearing. Conclusion: These data provide information about carrier frequency for SLC26A4 mutation-associated hearing loss and have important implications for genetic diagnostic testing for inherited deafness in the Korean population.

A role of pancreatic stellate cells in islet fibrosis and β-cell dysfunction in type 2 diabetes mellitus

Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Ahn, Yu-Bae,Song, Ki-Ho Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P><B>Objectives</B></P> <P>To investigate whether the activation of pancreatic stellate cells (PSCs) leads to pancreatic β-cell dysfunction in type 2 diabetes mellitus (T2DM).</P> <P><B>Methods</B></P> <P>The pancreases of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of T2DM, and patient with T2DM were analyzed. And the <I>in vitro</I> and <I>in vivo</I> effects of pirfenidone, an antifibrotic agent, on PSC activation, islet fibrosis, and β-cells were studied.</P> <P><B>Results</B></P> <P>The extent of islet fibrosis and the percentage of activated PSCs, positive for α-smooth muscle actin, in the islets were significantly greater in OLETF rats compared with non-diabetic rats. Also, the extent of islet fibrosis in patients with T2DM was slightly greater compared with age- and BMI-matched non-diabetic patients. In rat PSCs cultured with high glucose for 72 h, pirfenidone produced decreases in cell proliferation, release of collagen, and the expression of fibronectin and connective tissue growth factor. Treatment of OLETF rats with pirfenidone for 16 weeks decreased the activation of PSCs and the extent of islet fibrosis, but did not enhance glucose tolerance, pancreatic insulin content, or β-cell mass.</P> <P><B>Conclusions</B></P> <P>Activated PSCs in islets might lead to islet fibrosis in T2DM. However, PSC activation itself might not contribute significantly to progressive β-cell failure in T2DM.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Islet fibrosis developed progressively in OLETF rats, a model of type 2 diabetes. </LI> <LI> PSCs in the islets became activated in OLETF rats. </LI> <LI> Islet fibrosis was increased in patients with type 2 diabetes. </LI> <LI> Pirfenidone attenuated the activation of PSCs and islet fibrosis in OLETF rats. </LI> <LI> Pirfenidonet had no effects on glucose tolerance or on β-cells in OLETF rats. </LI> </UL> </P>

서해안 서천군 당정리 일대에 분포하는 육상 고해안 퇴적물의 형성 과정과 형성 시기(II): 추가 연대 자료 및 제4기 후기 연안 지형 발달 모델

신재열 ( Shin¸ Jae-ryul ),홍영민 ( Hong¸ Yeong-min ),류희경 ( Ryu¸ Hui-gyeong ),홍성찬 ( Hong¸ Seongchan ) 한국지형학회 2021 한국지형학회지 Vol.28 No.3

Following the previous study, we report a complementary dating data on the silty layers deposited in paleo-tidal conditions of the study area, Dangjeong-ri, Seocheon-gun and suggest coastal terrain development processes over the past 200,000 years. Based on the dating results, the silty layers distributed up to 25 m above mean sea level were deposited between 171 and 183 ka, and the gravel layer deposited in a fluvial environment of a paleo-Dangjeong stream was found to have formed between 78 and 83 ka. Considering relative altitudes of distribution, an uplift rate of the study area in the western coast is judged to be relatively 0.5~0.7 low to that of Pohang area in the eastern coast. Compared to Busan and Sacheon areas in the southern coast, it is assumed that an uplift rate of the study area shows a similar level with those during the late Quaternary.

Altered Secretory Pattern of Pancreatic Enzymes and Gastrointestinal Hormones in Streptozotocin-induced Diabetic Rats

Kim, Myung-Jun,Ryu, Gyeong-Ryul,Yi, Sae-Young,Min, Do-Sik,Rhie, Duck-Joo,Yoon, Shin-Hee,Hahn, Sang-June,Kim, Myung-Suk,Jo, Yang-Hyeok The Korean Society of Pharmacology 2002 The Korean Journal of Physiology & Pharmacology Vol.6 No.6

This study was performed to investigate the pancreatic exocrine dysfunction in streptozotocin- induced diabetic rats. Changes in pancreatic enzymes secretion and in pancreatic enzymes content were observed. The output and the tissue content of amylase were significantly reduced in diabetic rats, while the output and the content of lipase were increased. Plasma secretin and cholecystokinin (CCK) concentrations of diabetic rats were significantly increased compared to those of normal rats. The altered pancreatic exocrine function was abolished by the exogenous insulin administration. The exogenous insulin also restored the increased plasma secretin and CCK concentrations. From the above results, it is suggested that, in streptozotocin-induced diabetic rats, anticoordinated changes in pancreatic enzymes secretion as well as pancreatic enzymes content are attributable to insulin deficiency and that the insulin deficiency is responsible for the increased plasma concentrations of both secretin and CCK. However, it is not clear whether the elevated plasma secretin and CCK concentrations played a direct role in changes of pancreatic exocrine function.

Electrophysiological and Morphological Classification of Inhibitory Interneurons in Layer II/III of the Rat Visual Cortex

Rhie, Duck-Joo,Kang, Ho-Young,Ryu, Gyeong-Ryul,Kim, Myung-Jun,Yoon, Shin-Hee,Hahn, Sang-June,Min, Do-Sik,Jo, Yang-Hyeok,Kim, Myung-Suk The Korean Society of Pharmacology 2003 The Korean Journal of Physiology & Pharmacology Vol.7 No.6

Interneuron diversity is one of the key factors to hinder understanding the mechanism of cortical neural network functions even with their important roles. We characterized inhibitory interneurons in layer II/III of the rat primary visual cortex, using patch-clamp recording and confocal reconstruction, and classified inhibitory interneurons into fast spiking (FS), late spiking (LS), burst spiking (BS), and regular spiking non-pyramidal (RSNP) neurons according to their electrophysiological characteristics. Global parameters to identify inhibitory interneurons were resting membrane potential (>-70 mV) and action potential (AP) width (<0.9 msec at half amplitude). FS could be differentiated from LS, based on smaller amplitude of the AP (<∼50 mV) and shorter peak-to-trough time (P-T time) of the afterhyperpolarization (<4 msec). In addition to the shorter AP width, RSNP had the higher input resistance (>200 $M{Omega}$) and the shorter P-T time (<20 msec) than those of regular spiking pyramidal neurons. Confocal reconstruction of recorded cells revealed characteristic morphology of each subtype of inhibitory interneurons. Thus, our results provide at least four subtypes of inhibitory interneurons in layer II/III of the rat primary visual cortex and a classification scheme of inhibitory interneurons.

HNRNPA1, a Splicing Regulator, Is an Effective Target Protein for Cervical Cancer Detection: Comparison With Conventional Tumor Markers

Kim, Young-Jon,Kim, Byoung-Ryun,Ryu, Jae-Suk,Lee, Gyeong-Ok,Kim, Hak-Ryul,Choi, Keum-Ha,Ryu, Jae-Won,Na, Kyoung-Suk,Park, Min-Cheol,So, Hong-Seob,Cho, Ji-Hyun,Park, Do-Sim Blackwell Scientific Publications 2017 International journal of gynecological cancer Vol.27 No.2

<B>Objective</B><P>Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), serine/arginine-rich splicing factor 1 (SRSF1), and SRSF3 are splicing regulators associated with oncogenesis. However, the alterations of SF proteins and their diagnostic values in cervical cancer are unclear. To apply SFs clinically, effective marker selection and characterization of the target organ properties are essential.</P><B>Materials and Methods</B><P>We concurrently analyzed HNRNPA1, SRSF1, SRSF3, and the conventional tumor markers squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) in cervical tissue samples (n = 127) using semiquantitative immunoblotting. In addition, we compared them with p16 (cyclin-dependent kinase inhibitor 2A [CDKN2A]), which has shown high diagnostic efficacy in immunohistochemical staining studies and has been proposed as a candidate protein for point-of-care screening biochemical tests of cervical neoplasia.</P><B>Results</B><P>HNRNPA1, higher molecular weight forms of SRSF1 (SRSF1-HMws), SRSF3, CEA, and p16 levels were higher (<I>P</I> < 0.05) in cervical carcinoma tissue samples than in nontumoral cervical tissue samples. However, the levels of SRSF1-Total (sum of SRSF1-HMws and a lower molecular weight form of SRSF1) and SCCA, a commonly used cervical tumor marker, were not different between carcinoma and nontumoral tissue samples. In paired sample comparisons, HNRNPA1 (94%) showed the highest incidence of up-regulation (carcinoma/nontumor, >1.5) in cervical carcinoma, followed by p16 (84%), SRSF1-HMws (69%), SRSF3 (66%), CEA (66 %), SCCA (32%), and SRSF1-Total (31%). HNRNPA1 (92%) and p16 (91%) presented the two highest diagnostic accuracies for cervical carcinoma, which were superior to those of SRSF3 (75%), SRSF1-HMws (72%), CEA (72%), SCCA (59%), and SRSF1-Total (55%).</P><B>Conclusions</B><P>Our results identified that HNRNPA1 is the best diagnostic marker among the SFs and conventional markers given its excellent diagnostic efficacy for cervical carcinoma, and it has a p16-comparable diagnostic value. We suggest that HNRNPA1 is an additional effective target protein for developing cervical cancer detection tools.</P>

Electrophysiological and Morphological Classification of Inhibitory Interneurons in Layer II/III of the Rat Visual Cortex

Duck-Joo Rhie,Ho Young Kang,Gyeong Ryul Ryu,Myung-Jun Kim,Shin Hee Yoon,Sang June Hahn,Do Sik Min,Yang-Hyeok Jo,Myung-Suk Kim 대한생리학회-대한약리학회 2003 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

Interneuron diversity is one of the key factors to hinder understanding the mechanism of cortical neural network functions even with their important roles. We characterized inhibitory interneurons in layer II/III of the rat primary visual cortex, using patch-clamp recording and confocal reconstruction, and classified inhibitory interneurons into fast spiking (FS), late spiking (LS), burst spiking (BS), and regular spiking non-pyramidal (RSNP) neurons according to their electrophysiological characteristics. Global parameters to identify inhibitory interneurons were resting membrane potential (<FONT FACE= 바탕 >>⁣70 mV) and action potential (AP) width (<FONT FACE= 바탕 ><0.9 msec at half amplitude). FS could be differentiated from LS, based on smaller amplitude of the AP (<FONT FACE= 바탕 ><∼50 mV) and shorter peak-to-trough time (P-T time) of the afterhyperpolarization (<FONT FACE= 바탕 ><4 msec). In addition to the shorter AP width, RSNP had the higher input resistance (<FONT FACE= 바탕 >>200 M<FONT FACE= 바탕 >Ω) and the shorter P-T time (<FONT FACE= 바탕 ><20 msec) than those of regular spiking pyramidal neurons. Confocal reconstruction of recorded cells revealed characteristic morphology of each subtype of inhibitory interneurons. Thus, our results provide at least four subtypes of inhibitory interneurons in layer II/III of the rat primary visual cortex and a classification scheme of inhibitory interneurons.

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

Exendin‐4 inhibits iNOS expression at the protein level in LPS‐stimulated Raw264.7 macrophage by the activation of cAMP/PKA pathway

Chang, Seo‐,Yoon,Kim, Dong‐,Bin,Ryu, Gyeong Ryul,Ko, Seung‐,Hyun,Jeong, In‐,Kyung,Ahn, Yu‐,Bae,Jo, Yang‐,Hyeok,Kim, Myung‐,Jun Wiley Subscription Services, Inc., A Wiley Company 2013 Journal of cellular biochemistry Vol.114 No.4

<P><B>Abstract</B></P><P>Glucagon‐like peptide‐1 (GLP‐1) and its potent agonists have been widely studied in pancreatic islet β‐cells. However, GLP‐1 receptors are present in many extrapancreatic tissues including macrophages, and thus GLP‐1 may have diverse actions in these tissues and cells. Therefore, we examined the mechanism by which exendin‐4 (EX‐4), a potent GLP‐1 receptor agonist, inhibits lipopolysaccharide (LPS)‐induced iNOS expression in Raw264.7 macrophage cells. EX‐4 significantly inhibited LPS‐induced iNOS protein expression and nitrite production. However, Northern blot and promoter analyses demonstrated that EX‐4 did not inhibit LPS‐induced iNOS mRNA expression and iNOS promoter activity. Electrophoretic mobility shift assay (EMSA) showed that EX‐4 did not alter the binding activity of NF‐κB to the iNOS promoter. Consistent with the result of EMSA, LPS‐induced IκBα phosphorylation and nuclear translocation of p65 were not inhibited by EX‐4. Also, actinomycin D chase study and the promoter assay using the construct containing 3′‐untranslated region of iNOS showed that EX‐4 did not affect iNOS mRNA stability. Meanwhile, cycloheximide chase study demonstrated that EX‐4 significantly accelerated iNOS protein degradation. The EX‐4 inhibition of LPS‐induced iNOS protein was significantly reversed by adenylate cyclase inhibitors (MDL‐12330A and SQ 22536), a PKA inhibitor (H‐89) and PKAα gene silencing. These findings suggest that EX‐4 inhibited LPS‐induced iNOS expression at protein level, but not at transcriptional mechanism of iNOS gene and this inhibitory effect of EX‐4 was mainly dependent on cAMP/PKA system. J. Cell. Biochem. 114: 844–853, 2013. © 2012 Wiley Periodicals, Inc.</P>