The angiotensin II type 2 receptors protect renal tubule mitochondria in early stages of diabetes mellitus
Diabetic nephropathy correlates more closely to defective mitochondria and increased oxidative stress in the kidney than to hyperglycemia. A key driving factor of diabetic nephropathy is angiotensin II acting via the G-protein-coupled cell membrane type 1 receptor. The present study aimed to investi...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
4 September 2018
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| In: |
Kidney international
Year: 2018, Volume: 94, Issue: 5, Pages: 937-950 |
| ISSN: | 1523-1755 |
| DOI: | 10.1016/j.kint.2018.06.006 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.kint.2018.06.006
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| Author Notes: | Tamara Micakovic, Stamatia Papagiannarou, Euan Clark, Yalcin Kuzay, Katarina Abramovic, Jörg Peters, Carsten Sticht, Nadine Volk, Thomas Fleming, Peter Nawroth, Hans-Peter Hammes, Natalia Alenina, Hermann-Josef Gröne and Sigrid Christa Hoffmann |
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| 245 | 1 | 4 | |a The angiotensin II type 2 receptors protect renal tubule mitochondria in early stages of diabetes mellitus |c Tamara Micakovic, Stamatia Papagiannarou, Euan Clark, Yalcin Kuzay, Katarina Abramovic, Jörg Peters, Carsten Sticht, Nadine Volk, Thomas Fleming, Peter Nawroth, Hans-Peter Hammes, Natalia Alenina, Hermann-Josef Gröne and Sigrid Christa Hoffmann |
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| 520 | |a Diabetic nephropathy correlates more closely to defective mitochondria and increased oxidative stress in the kidney than to hyperglycemia. A key driving factor of diabetic nephropathy is angiotensin II acting via the G-protein-coupled cell membrane type 1 receptor. The present study aimed to investigate the role of the angiotensin II type 2 receptor (AT2R) at the early stages of diabetic nephropathy. Using receptor binding studies and immunohistochemistry we found that the mitochondria in renal tubules contain high-affinity AT2Rs. Increased renal mitochondrial AT2R density by transgenic overexpression was associated with reduced superoxide production of isolated mitochondria from non-diabetic rats. Streptozotocin-induced diabetes (28 days) caused a drop in the ATP/oxygen ratio and an increase in the superoxide production of isolated renal mitochondria from wild-type diabetic rats. This correlated with changes in the renal expression profile and increased tubular epithelial cell proliferation. AT2R overexpression in tubular epithelial cells inhibited all diabetes-induced renal changes including a drop in mitochondrial bioenergetics efficiency, a rise in mitochondrial superoxide production, metabolic reprogramming, and increased proliferation. Thus, AT2Rs translocate to mitochondria and can contribute to reno-protective effects at early stages of diabetes. Hence, targeted AT2R overexpression in renal cells may open new avenues to develop novel types of drugs preventing diabetic nephropathy. | ||
| 650 | 4 | |a Adenosine Triphosphate | |
| 650 | 4 | |a angiotensin | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Cell Proliferation | |
| 650 | 4 | |a Diabetes Mellitus, Experimental | |
| 650 | 4 | |a Diabetic Nephropathies | |
| 650 | 4 | |a diabetic nephropathy | |
| 650 | 4 | |a Gene Expression Profiling | |
| 650 | 4 | |a Kidney Tubules | |
| 650 | 4 | |a Male | |
| 650 | 4 | |a mitochondria | |
| 650 | 4 | |a Mitochondria | |
| 650 | 4 | |a oxidative stress | |
| 650 | 4 | |a Rats | |
| 650 | 4 | |a Reactive Oxygen Species | |
| 650 | 4 | |a Receptor, Angiotensin, Type 2 | |
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