Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy
BackgroundCeramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podoc...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Diabetes Association
2020-08-01
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| Series: | Diabetes & Metabolism Journal |
| Subjects: | |
| Online Access: | http://e-dmj.org/upload/pdf/dmj-44-581.pdf |
| _version_ | 1819159488820674560 |
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| author | Chang-Yun Woo Ji Yeon Baek Ah-Ram Kim Chung Hwan Hong Ji Eun Yoon Hyoun Sik Kim Hyun Ju Yoo Tae-Sik Park Ranjan Kc Ki-Up Lee Eun Hee Koh |
| author_facet | Chang-Yun Woo Ji Yeon Baek Ah-Ram Kim Chung Hwan Hong Ji Eun Yoon Hyoun Sik Kim Hyun Ju Yoo Tae-Sik Park Ranjan Kc Ki-Up Lee Eun Hee Koh |
| author_sort | Chang-Yun Woo |
| collection | DOAJ |
| description | BackgroundCeramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy.MethodsWe used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes.ResultsOLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity.ConclusionWe showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease. |
| first_indexed | 2024-12-22T16:41:21Z |
| format | Article |
| id | doaj.art-68cda39f39754057803a57a4f5d43be5 |
| institution | Directory Open Access Journal |
| issn | 2233-6079 2233-6087 |
| language | English |
| last_indexed | 2024-12-22T16:41:21Z |
| publishDate | 2020-08-01 |
| publisher | Korean Diabetes Association |
| record_format | Article |
| series | Diabetes & Metabolism Journal |
| spelling | doaj.art-68cda39f39754057803a57a4f5d43be52022-12-21T18:19:51ZengKorean Diabetes AssociationDiabetes & Metabolism Journal2233-60792233-60872020-08-0144458159110.4093/dmj.2019.00631737Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic NephropathyChang-Yun Woo0Ji Yeon Baek1Ah-Ram Kim2Chung Hwan Hong3Ji Eun Yoon4Hyoun Sik Kim5Hyun Ju Yoo6Tae-Sik Park7Ranjan Kc8Ki-Up Lee9Eun Hee Koh10Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Internal Medicine, University of Ulsan College of Medicine, Seoul, .KoreaAsan Institute for Life Science, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Medical Science and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Medical Science and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, .KoreaAsan Institute for Life Science, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Medical Science and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Life Science, Gachon University, Seongnam, .KoreaAsan Institute for Life Science, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Internal Medicine, University of Ulsan College of Medicine, Seoul, .KoreaDepartment of Internal Medicine, University of Ulsan College of Medicine, Seoul, .KoreaBackgroundCeramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy.MethodsWe used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes.ResultsOLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination [GFA]) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity.ConclusionWe showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.http://e-dmj.org/upload/pdf/dmj-44-581.pdfdiabetic nephropathiesceramidesmitochondriapodocytesreactive oxygen speciesthermozymocidin |
| spellingShingle | Chang-Yun Woo Ji Yeon Baek Ah-Ram Kim Chung Hwan Hong Ji Eun Yoon Hyoun Sik Kim Hyun Ju Yoo Tae-Sik Park Ranjan Kc Ki-Up Lee Eun Hee Koh Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy Diabetes & Metabolism Journal diabetic nephropathies ceramides mitochondria podocytes reactive oxygen species thermozymocidin |
| title | Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy |
| title_full | Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy |
| title_fullStr | Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy |
| title_full_unstemmed | Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy |
| title_short | Inhibition of Ceramide Accumulation in Podocytes by Myriocin Prevents Diabetic Nephropathy |
| title_sort | inhibition of ceramide accumulation in podocytes by myriocin prevents diabetic nephropathy |
| topic | diabetic nephropathies ceramides mitochondria podocytes reactive oxygen species thermozymocidin |
| url | http://e-dmj.org/upload/pdf/dmj-44-581.pdf |
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