Angiotensin‐converting enzyme inhibitors attenuated advanced glycation end products‐induced renal tubular hypertrophy via enhancing nitric oxide signaling
| Autor: | Yao‐Bin Liu, Wei-Chih Kan, Jean-Yu Hwang, Jinn-Yuh Guh, Jau-Shyang Huang, Lea-Yea Chuang, Yu-Lin Yang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Glycation End Products
Advanced 0301 basic medicine MAPK/ERK pathway Captopril MAP Kinase Signaling System Physiology Clinical Biochemistry Nitric Oxide Synthase Type II Angiotensin-Converting Enzyme Inhibitors Cell Enlargement S-Nitroso-N-Acetylpenicillamine Pharmacology Nitric Oxide Cell Line Nitric oxide Kidney Tubules Proximal 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Enalapril Glycation Cyclic GMP-Dependent Protein Kinases medicine Humans Nitric Oxide Donors cardiovascular diseases Protein kinase A Cyclic GMP biology Angiotensin-converting enzyme Hypertrophy Cell Biology Thionucleotides Angiotensin II Enzyme Activation 030104 developmental biology chemistry 030220 oncology & carcinogenesis biology.protein Signal Transduction medicine.drug |
| Zdroj: | Journal of Cellular Physiology. 234:17473-17481 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.28369 |
| Popis: | Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3',5'-cyclic monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the PKG activator 8-para-chlorophenylthio-cGMPs (8-pCPT-cGMPs). In addition, AGE-enhanced activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8-pCPT-cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE-induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8-pCPT-cGMPs decreased protein levels of fibronectin, p21 Waf1/Cip1 , and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE-increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway. |
| Databáze: | OpenAIRE |
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