• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.567-575
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• 2018

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

• 대한의생명과학회지
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• 제24권4호
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• pp.285-291
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• 2018

Gremlin-1 (GREM1) has been defined as an antagonist of bone morphogenetic proteins (BMPs), particularly during embryonic development and tissue differentiation. However, recent studies have shown that GREM1 has BMPs-dependent or -independent functions in diverse human diseases. GREM1 plays a key role in the process of organ fibrosis, including lungs, kidneys, and so on. The GREM1-induced fibrosis typically promotes the development of other diseases, such as pulmonary hypertension, renal inflammation, and diabetic nephropathy. More recently, considerable evidence has been reported showing that GREM1 is involved in the promotion and/or progression of tumors in vitro and in vivo. It also performs an oncogenic role in the maintenance of cancer stem cells. Although GREM1 is known to function in a variety of diseases, here we focus on the role of GREM1 in cancer, and suggest GREM1 as a potential therapeutic target in certain types of cancer.

• Applied Microscopy
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• 제17권1호
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• pp.47-64
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• 1987

Morphological difference of the renal glomerulus at different age groups have been studied in young (three month-old), adult (twelve month-old) and old (thirty month-old) Fisher strain 344 rats. Pieces of the tissues were taken from renal corticies prefixed with 2.5% glutaraldehyde-1.5% paraformaldehyde (0.1 M Millonig's phosphate buffer, pH 7.3), following by post-fixation with 1% osmium tetroxide (0.1 M Millonig's phosphate buffer, pH 7.3) and embedded within Araldite. The ultrathin sections contrasted with uranyl acetate and lead citrate were observed under a JEM 100CX electron microscope. The mean thickness of glomerular basal lamina and Bowman's capsule were determined by measuring the thinnest portion of basal lamina, and by taking the average of 50 readings from electron micrographs at different ages. The numerical changes of the slit pores were compared based upon the numbers over the length of 10um of glomerular basal lamina. The results were as follow: 1. The thickness of glomerular basal lamina is increased during aging; 140.4 nm in young rats, 270.0 nm in adult ones, and 437.8 nm in old ones. 2. The thickness of basal lamina of parietal cells of Bowman's capsule is 187.5 nm in young rats, 914.0 nm in adult ones, and 2850.0 nm in old ones. 3. The numbers of the slit pores of basal lamina are reduced during aging, 30.3 slit pores/$10{\mu}m$ in adult ones, and 24.2 slit pores/$10{\mu}m$ in old ones. 4. Accumulation of dense intracytoplasmic filamentous material in the parietal cells of Bowman's capsule is increased in the vicinity of the basal lamina during aging. The proximal tubule-like epithelial cell in Bowman's capsule is observed at one glomerulus in a young rat. 5. The endothelial cells are edematous and form balloon-like structure protruding into capillary lumen in young and old rats. 6. Cytoplasm of the podocyte shows a variety of alteration during aging, such as swelling of mitochondria and of endoplasmic reticulum, and increase of microtubules, microfilaments, lysosomes and lamellated myelin structures, etc. Accumulation of dense intracytoplasmic material in the foot processes is increased in the vicinity of the basal lamina during aging. The podocytic membrane-like structures are seen in young and o]d rats. 7. The mesangial matrices and mesangial cells are increased during aging, and slight swelling of endoplasmic reticulum and Golgi cisternae in young and old rats.

• Preventive Nutrition and Food Science
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• 제13권2호
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• pp.84-89
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• 2008

This study was designed to investigate the protective effect of a methanol extract of Chungkookjang (CKJ) on high glucose induced oxidative stress in LLC-$PK_1$ cells (renal tubular epithelial cells), which are susceptible to oxidative stress. Freeze dried CKJ powder was extracted with methanol, and the extract solution was concentrated, and then used in this study. To determine the protective effect of CKJ extract, oxidative stress was induced by exposing of LLC-$PK_1$ cells to high glucose (30 mM) or normal glucose (5 mM) for 24 hr. Exposure of LLC-$PK_1$ cells to high glucose for 24 hr resulted in a significant (p<0.05) decrease in cell viability, catalase, SOD and GSH-px activity and a significant (p<0.05) increase in intracellular ROS level and thiobarbituric acid reactive substances (TBARS) formation in comparison to the cells treated with 5 mM glucose. CKJ extract treatment decreased intracellular ROS level and TBARS formation, and increased cell viability and activities of antioxidant enzymes including catalase, SOD and GSH-px in high glucose pretreated LLC-$PK_1$ cells. These results suggest that CKJ extract may be able to protect LLC-$PK_1$ cells from high glucose-induced oxidative stress, partially through the antioxidative defense systems.

• The Korean Journal of Physiology and Pharmacology
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• 제8권3호
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• pp.117-127
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• 2004

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

• 환경생물
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• 제22권1호
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• pp.133-140
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• 2004

유기주석화합물이 넙치의 기관계 구조에 미치는 독성을 알아보기 위하여 넙치를 대조구와 TBTO를 첨가한 6개 농도구(0.17, 0.36, 0.60, 3.20, 6.30, 12.50 ${\mu}g \;L^{-1}$)에서 42일 동안 노출 실험을 하였다. 조직상의 변화 정도는 노출 시간과 TBTO농도의 증가에 따라 심하게 나타났다. 저농도의 TBTO 노출구에서 관찰된 초기 조직학적 변화로는 아가미에서는 점액세포와 염세포의 활성, 새판 모세혈관의 충혈, 상피층의 비후, 간췌장에서는 간세포의 활성화와 췌장 효소원과립의 감소, 담관의 변성이 확인되었으며, 신장에서는 모세혈관의 충혈, 호산성세포와 혹색 대식세포군의 출현이 관찰되었다. 고농도의 TBTO 노출구에서 관찰된 조직학적 변화로는 아가미에서는 새판 상피층의 박리와 새판의 붕괴, 간췌장에서는 간세포의 핵응축, 세포질의 혼탁 및 과립변성, 신장에서는 조혈세포의 핵응축, 사구체와 세뇨관의 붕괴 등 정상적인 기능 수행이 어려울 것으로 판단되는 조직상들이 관찰되었다. 이와 같은 결과는 TBTO는 다른 수중오염원과 마찬가지로 어류 기관계의 조직병리학적 변화를 유도한다는 것을 나타낸다.

• Journal of Ginseng Research
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• 제36권3호
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• pp.256-262
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• 2012

Reactive oxygen species play critical role in kidney damage. Free radical-scavenging activities of Panax ginseng are known to be increased by heat-processing. The structural change of ginsenoside and the generation of Maillard reaction products (MRPs) are closely related to the increased free radical-scavenging activities. In the present study, we have demonstrated the Maillard reaction model experiment using ginsenoside Re and glycine mixture to identify the renoprotective effect of MRPs from ginseng or ginsenosides. Ginsenoside Re was transformed into less-polar ginsenosides, namely Rg2, Rg6 and F4 by heat-processing. The free radical-scavenging activity of ginsenoside Re-glycine mixture was increased in a temperature-dependant manner by heatprocessing. The improved free radical-scavenging activity by heat-processing was mediated by the generation of antioxidant MRPs which led to the protection of LLC-PK1 renal epithelial cells from oxidative stress. Although the free radical scavenging activities of less-polar ginsenosides were weak, they could protect LLC-PK1 cells from oxidative stress. Therefore, MRPs and less-polar ginsenosides contributed to the combined renoprotective effects against oxidative renal damage.

• 대한의생명과학회지
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• 제14권4호
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• pp.211-218
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• 2008

The purpose of this study was to investigate the effects of dietary Chungkookjang (Korean fermented soybean) powder on blood glucose level, lipid profiles, antioxidant enzymes activities and histological changes in kidney of streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats of three groups including nondiabetic group fed normal diet (NC), diabetic group fed normal diet (DC) and diabetic group fed Chungkookjang diet (DCH; 100 g/kg diet) were reared for 8 weeks. The serum glucose, triglycelide and total lipid levels in the DCH group were significantly lower (P<0.05) than the DC group. The renal xanthine oxidase, catalase and glutathione S-transferase activities in the DC group were significantly higher than the NC group. The xanthine oxidase, superoxide dismutase and glutathione S-transferase activities in the DCH group were significantly lower than the DC group (P<0.05). Tubular epithelial change, such as Armanni-Ebstein cells, was significantly reduced in the DCH group compared to the DC group. In conclusion, these results indicated that Chungkookjang supplement seems to be beneficial to correct the hyperglycemia and hyperlipidemia as well as to protect kidney against diabetic changes.

• Journal of Acupuncture Research
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• 제15권2호
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• pp.331-348
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• 1998

Purpose: In order to study the therapeutic effect of TBR(Smilacis glabrae Rhizoma) aqua-acupuncture on the $HgCI_2$(mercury bichloride) intoxicated kidneys of rats. Methods: 10% TBR extract solution was aqua-punctured into the bilateral loci of Shin-su(BL23), every other day for 18 days, and the amount of leucocytes, erythrocytes, thrombocytes, hematocrit, hemoglobin, serum BUN and creatinine levels were measured and renal mercury level and histopathological findings were studied as well. The experimental groups were into nonmaI group, control group, sample I group, sample II group and sample III group. Results: 1. There were not any significant changes of leucocytes, erythrocytes and serum creatinine level in the TBR aqua-acupuncture group, saline aqua-acupuncture group and TBR aqua-acupuncture group respectively as compared with control group. 2. It showed a significant increase of hematocrit and hemoglobin level in the TBR aqua-acupuncture group on the 8th experimental day as compared with the control group. 3. It showed a significant increase of platelet in the TBR aqua-acupuncture group on the 8th experimental day, whereas significant decreases on the 18th experimental day as compared with the control group. 4. It showed a significant decrease of serum BUN level in the TBR aqua-acupuncture group on the 8th and 18th experimental day as compared with the control group. 5. It showed a significant decrease of renal mercury level in the TBR aqua-acupuncture group on compared with the control group. 6. In the histopathological findings, TBR aqua-acupuncture group showed slight atrophy of the renal tubules, mitosis and regeneration of tubular lining cells with visible nuclei, whereas the control group showed acute tubular necrosis, especially severe necrosis of tubular epithelial cells. Conclusions: Smilacis glabrae Rhizoma aqua-acupuncture on injured kidneys Induced by HgCl2 Intoxication in Rats increases hematocrit, hemoglobin and platelet level, and decreases BUN, renal mercury level. This suggests that Smilacis glabrae Rhizoma aqua-acupuncture helps to recover kidney from HgCl2 intoxication.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.599-610
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• 2023

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.