Role of Podocyte AMP Kinase

하태선 충북대학교 동물의학연구소 2011 Journal of Biomedical and Translational Research Vol.12 No.3

AMP-activated protein kinase (AMPK), as a sensor of cellular energy status, has been known to play an important role in the pathophysiology of diabetes and its complications. As AMPK is also expressed in podocytes, it is possible that podocyte AMPK would be an important contributing factor in the development of proteinuria. In recent years, although interest regarding AMPK in the kidney has intensified, the studies on the role of AMPK in podocytes are limited. In this review, I will discuss the roles of AMPK in podocytes, which may involve in the development of podocyte dysfunction and proteinuria, and the possibility of AMPK-modulating drugs in the prevention and treatment of podocytopathy.

Angiotensin II induces endoplasmic reticulum stress in podocyte, which would be further augmented by PI3-kinase inhibition

하태선,박혜영,성수빈,안희열 대한고혈압학회 2015 Clinical Hypertension Vol.21 No.12

Introduction: Angiotensin II (Ang II) contributes to the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. On renal effects, Ang II plays an important role in the development of proteinuria and glomerulosclerosis by the modification of podocyte molecules and cell survival. In the present study, we investigated the effect of Ang II on endoplasmic reticulum (ER) stress in podocytes. Methods: We cultured mouse podocytes with increasing doses of Ang II and evaluated ER stress markers by Western blotting. Results: Ang II increased Bip protein, an ER chaperone, in a dose-dependent manner at 24 h, which was ameliorated by losartan, an angiotensin II type 1 receptor antagonist. Ang II also increased ER stress markers, such as phospho-PERK, phospho-eIF2α, and ATF4 proteins of podocyte, significantly in a dose-dependent manner at 24 h. Increased phospho-PERK and ATF4 proteins were further augmented by phosphoinositide 3 (PI3)-kinase inhibitor, LY294002, which suggested that Ang II could induce podocyte ER stress of PERK-eIF2α-ATF4 axis via PI3-kinase pathway. Discussion: These studies suggest that Ang II could induce podocyte ER stress of PERK-eIF2α-ATF4 axis via PI3-kinase pathway, which would contribute to the development of podocyte injury induced by Ang II, and the augmentation of PI3-kinase would be a therapeutic target.

신 사구체 상피세포의 배양과 응용: Ⅰ. 사구체 상피세포의 배양

하태선 충북대학교 의과대학 충북대학교 의학연구소 1997 忠北醫大學術誌 Vol.7 No.2

신장의 각 세포의 생체의 실험을 위해선 사구체나 세뇨관의 분리, 배양을 통한 각 구성세포의 배양실험으로서 다음과 같은 방향으로 연구가 향하고 있다. 즉, 생체내의 주위세포나 환경들을 모두 제거한 상태에서의 특정 세포의 생리적 혹은, 생화학적 기능 등을 연구할 수 있다 또한, 관련 사구체나 세뇨관 간질의 신 질환연구를 위하여 질환의 병태생리에 각 세포들이 어떠한 기전으로 기여하는지를 연구할 수 있고, 이를 통하여 치료방법의 연구에도 응용할 수 있다. 사구체 상피세포도 마찬가지로 배양을 통하여 전술한 여러 방향의 연구를 하고 있다. 본 연구자는 여러 연구자의 논문고찰과 저자의 경험을 토대로 사구체 상피세포의 배양과 문제점 등에 대해 고찰하였다. For the evaluation of the roles of glomerular epithelial cells on physiologic or pathophysiologic events in normal or pathologic conditions, one can use the in vitro model in addition to the in vivo model. Visceral epithelial cells(VECs) have been investigated in the role of glomerular permeability and biomechanical function. For the parietal epithelial cells(PECs), these cells have been known to have a structural role within Bowman's capsule. Additionally, as PECs also play an important role in the progression of crescentic glomerulonephritis, cultured and characterized PECs can be used for the elucidation of the pathophysiologic role as an in vitro model. The author reviewed the in vitro culture the evaluation of the functions of both VECs and PECs.

신사구체 상피세포의 배양과 응용 : Ⅱ. 사구체 상피세포배양의 응용

하태선 충북대학교 의과대학 충북대학교 의학연구소 1998 忠北醫大學術誌 Vol.8 No.1

사구체 상피세포는 내장상피세포와 벽측상피세포가 있는데 이들은 그 동안 기저막과 함께 사구체여과구조를 이루거나 보우만주머니를 유지하는 기능적인 연구뿐만 아니라 여러 신 질환의 병태생리에 관한 연구들이 이루어졌다. 즉, 여러 신 질환의 발생과 진행과정중 이차적인 영향을 받아서 족돌기 수축, 내장상피세포의 부분적 박리, 사구체 기저막의 소실, 보우만주머니와의 유착, 경화증 등을 초래하는 것으로 알려졌다. 그러나 최근에는 조직학적 소견과 생화학적 연구결과로서 여러 신 질환의 병태생리과정에서 일차적으로 내장상피세포의 역학적인 구조유지기능의 소실도 관여하는 것으로 알려지게 되었다. 이러한 신장의 사구체 상피세포에 관한 생리적 혹은, 생화학적 기능연구는 배양을 통한 생체외 실험으로도 연구할 수 있고, 또한, 사구체 상피세포와 관련된 신 사구체질환, 예를 들면, 미세변화성 신증후군이나 초점성 분절성 사구체경화증, 막성 사구체신염, 반월체 사구체신염 등의 병태생리에 사구체상피세포가 어떠한 세포 특이적인 기전으로 기여하는지를 연구할 수 있으며 이를 통하여 치료방법의 연구에도 응용할 수 있다. 이에 본 연구자는 여러 연구자의 논문고찰과 저자의 경험을 토대로 사구체 상피세포의 배양에 이어서 응용방향에 대해 고찰하였다. To evaluate the roles of glomerular epithelial cells, visceral and parietal, we can use the in vitro model in addition to in vivo model. Visceral epithelial cells(VECs) have been investigated in the view of glomerular permeability. Moreover, VECs also has important roles in the initiation and progression of many glomerular diseases, including glomerulosclerosis. In the case of parietal epithelial cells(PECs), these cells have been known as structural role on Bowman's capsule. However, PECs also played an important role on the progression of crescentic glomerulonephritis. The author reviewed the recently re-evaluated roles of both VECs and PECs and introduced the cell culture model of these cells as an applicable method.

대학생의 음료섭취 실태와 식품섭취 및 영양소섭취와의 관련성에 관한 연구

하태선,박명희,최영선,조성희 대한영양사협회 1999 대한영양사협회 학술지 Vol.5 No.1

This study was conducted to investigate beverage consumptions in relation to food intakes of Korean young people. One hundred thirty five college students(61 males and 74 females) living in Taegu, Kyung-buk and Taejon answered to questionnaires and recorded three day food intakes between May 20 and June 5. 1997. The preferred beverages were fruit juice, carbonated drink, dairy drink, sport beverage for male students, and fruit juice, dairy drink, sport beverage and carbonated drink for female students. Beverage taken most frequently was coffee for both. Frequent consumption of orange juice was associated with consumption of vegetables, meats, and fats and oils used for frying, and light cola seemed to be consumed with greasy dishes. Beverage consumption contributed to intakes of calcium and vitamin B_2 more than other nutrients. 4.6% of total energy intake, 12.5% of calcium intake, 7.9% of vitamin B_2 were provided from beverages in males, and 4.8% of total energy intake, 15.5% of calcium intake, 11.4% of vitamin B_2 provided from beverages in females. Contributions of beverages to nutrient intakes were higher in female than in male students. Calcium intake was the lowest among nutrients for males, and intakes of iron and vitamin A were the lowest for females as compared to the recommended dietary allowances. Therefore it is necessary to guide college students to choose beverages for balanced intakes of necessary nutrients.

ACTS 신학·신앙운동으로서의 기독교사회복지실천의 방향

하태선 아신대학교 ACTS 신학연구소 2023 ACTS 신학저널 Vol.55 No.-

The purpose of this study is to understanding the the theological synoptic movement as an ACTS theology-faith movement and to explore the future direction of Christian social welfare practice based on the central Christian truth. First, The Christian social welfare practice of ACTS should be a practice to restore the image of God. Second, The Christian social welfare practice of ACTS can be realized in the redemption of spirit and body through Jesus Christ based on the redemptive work of Jesus Christ. Third, Christian social welfare practice of ACTS should be a practice for world evangelization. Therefore, the Christian social welfare practice of ACTS must practice God’s love for human beings through concrete care and to solve social problems broken by sin, and ultimately pursue welfare that is realized only through the redemption of Jesus Christ. 본 논문은 ACTS 신학·신앙운동으로 신학공관 운동을 이해하고, ACTS가 지향하는 기독교 중심진리 내용을 고찰한 후, 기독교의 중심진리에 근거한 기독교사회복지실천의 나아갈 방향을 모색하기 위한 연구이다. ACTS의 기독교사회복지실천이 나아가야 할 방향을 정리하면 다음과 같다. 첫째, ACTS의 기독교사회복지실천은 하나님의 형상을 회복하기 위한 실천이 되어야 한다. 둘째, ACTS의 기독교사회복지실천은 예수그리스도의 구속사역에 기반하여 예수그리스도를 통한 영과 육의 구속에서 실현될 수 있다. 셋째, ACTS의 기독교사회복지실천은 세계복음화를위한 실천이 되어야 한다. 따라서 ACTS의 기독교사회복지실천은 인간을 향한 하나님의 사랑이 구체적인 돌봄과 실천으로 구현되어야 하며, 죄로인해 깨어진 사회문제를 해결하고, 궁극적으로 예수그리스도의 구속으로만 실현되는 복지를 추구해야 할 것이다.

신사구체 세포배양

하태선 충북대학교 의과대학 충북대학교 의학연구소 1995 忠北醫大學術誌 Vol.5 No.1

신장의 사구체나 사구체 각세포의 기능연구와 관련 사구체 신질환의 연구를 위하여 생체내 실험뿐만 아니라 생체외 실험의 도입이 필요하게 되었다. 이를 위하여 사구체의 분리와 배양법이 연구되고 있는데 대상동물과 배양하고자 하는 세포에 따라, 또는, 목적하고자 하는 실험을 위하여 이상적인 배양조건을 찾고자 하고 있다. 한편, 이러한 사구체 세포배양의 연구에 있어서도 성상확인등의 문제점들이 발견되어 이를 해결하려고 하고 있다. 본 연구자는 여러 연구자의 논문고찰과 저자의 경험을 토대로 최근 사구체 구성세포들의 연구에 많이 응용되고 있는 세포배양의 방법, 성상확인, 문제점 등에 대해 고찰하였다. Coincident with trends in other areas of biologic research, there has been a growing interest by investigative nephrologists in the use of tissue culture techniques for the studies of the function of individual cells and their roles in the pathophysiology of various related glomerular diseases. Many investigators have tried to find the ideal methods for each cells or target studies and gained many available results. However, some problems have been noted by other authors. The author reviewed the methodology, characterization tools, and problematic areas in glomerular cell culture from the informations of many other reports and experiences including self-experiences.

Angiotensin II Modulates p130Cas of Podocytes by the Suppression of AMP-Activated Protein Kinase

하태선,박혜영,성수빈,안희열 대한의학회 2016 Journal of Korean medical science Vol.31 No.4

Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into perinuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.

Ginseng total saponin modulates podocyte p130Cas in diabetic condition

하태선,이진석,최지영,박혜영 고려인삼학회 2013 Journal of Ginseng Research Vol.37 No.1

Proteinuric conditions demonstrate structural and compositional changes of the foot processes and slit diaphragms betweenpodocytes. p130Cas in podocytes serves as an adapter protein anchoring glomerular basement membrane to actin filaments ofpodocyte cytoskeleton. To investigate the effect of ginseng total saponin (GTS) on the pathologic changes of podocyte p130Casinduced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, control); 2) high glucose (HG,30 mM); 3) advanced glycosylation endproducts (AGE)-added; or 4) HG plus AGE-added conditions and treated with GTS. In confocal imaging, p130Cas colocalized with zonula occludens-1 and synaptopodin connecting to F-actin. However, diabeticconditions relocalized p130Cas molecules at perinuclear cytoplasmic area and reduced the intensity of p130Cas. In Westernblotting, diabetic conditions, especially HG plus AGE-added condition, decreased cellular p130Cas protein levels at 24 and 48h. GTS improved such quantitative and qualitative changes. These findings imply that HG and AGE have an influence on theredistribution and amount of p130Cas of podocytes, which can be reversed by GTS.

Ginseng Total Saponin Improves Podocyte Hyperpermeability Induced by High Glucose and Advanced Glycosylation Endproducts

하태선,최지영,박혜영,이진석 대한의학회 2011 Journal of Korean medical science Vol.26 No.10

Early diabetic nephropathy is characterized by glomerular hyperpermeability as a result of impaired glomerular filtration structure caused by hyperglycemia, glycated proteins or irreversible advanced glycosylation endproducts (AGE). To investigate the effect of ginseng total saponin (GTS) on the pathologic changes of podocyte ZO (zonula occludens)-1 protein and podocyte permeability induced by diabetic conditions, we cultured mouse podocytes under: 1) normal glucose (5 mM, = control); 2) high glucose (HG, 30 mM); 3) AGE-added;or 4) HG plus AGE-added conditions and treated with GTS. HG and AGE increased the dextran filtration of monolayered podocytes at early stage (2-8 hr) in permeability assay. In confocal imaging, ZO-1 colocalized with actin filaments and β-catenin at cell contact areas, forming intercellular filtration gaps. However, these diabetic conditions suppressed ZO-1 immunostainings and disrupted the linearity of ZO-1. In Western blotting, diabetic conditions also decreased cellular ZO-1 protein levels at 6 hr and 24 hr. GTS improved such quantitative and qualitative changes. These findings imply that HG and AGE have an influence on the redistribution and amount of ZO-1 protein of podocytes thereby causing hyperpermeability at early stage, which can be reversed by GTS.