Cinnamaldehyde and Nitric Oxide Attenuate Advanced Glycation End Products‐Induced the JAK/STAT Signaling in Human Renal Tubular Cells
Autor: | Jau-Shyang Huang, Lea-Yea Chuang, Jinn-Yuh Guh, Ying-Ho Lee, Jean-Yu Hwang |
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Rok vydání: | 2015 |
Předmět: |
Glycation End Products
Advanced STAT3 Transcription Factor medicine.medical_specialty Cell Survival Cinnamomum osmophloeum S-Nitroso-N-Acetylpenicillamine Pharmacology Nitric Oxide Biochemistry Cinnamaldehyde stat Cell Line RAGE (receptor) Nitric oxide chemistry.chemical_compound Glycation Internal medicine medicine Humans Nitric Oxide Donors Acrolein STAT3 Molecular Biology biology Cell Biology Janus Kinase 2 biology.organism_classification In vitro Kidney Tubules STAT1 Transcription Factor Endocrinology chemistry biology.protein Signal Transduction |
Zdroj: | Journal of Cellular Biochemistry. 116:1028-1038 |
ISSN: | 1097-4644 0730-2312 |
DOI: | 10.1002/jcb.25058 |
Popis: | Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. It possesses anti-diabetic properties in vitro and in vivo and has anti-inflammatory and anti-cancer effects. To explore whether cinnamaldehyde was linked to altered advanced glycation end products (AGE)-mediated diabetic nephropathy, the molecular mechanisms of cinnamaldehyde responsible for inhibition of AGE-reduced nitric oxide (NO) bioactivity in human renal proximal tubular cells were examined. We found that raising the ambient AGE concentration causes a dose-dependent decrease in NO generation. Cinnamaldehyde significantly reverses AGE-inhibited NO generation and induces high levels of cGMP synthesis and PKG activation. Treatments with cinnamaldehyde, the NO donor S-nitroso-N-acetylpenicillamine, and the JAK2 inhibitor AG490 markedly attenuated AGE-inhibited NOS protein levels and NO generation. Moreover, AGE-induced the JAK2-STAT1/STAT3 activation, RAGE/p27(Kip1) /collagen IV protein levels, and cellular hypertrophy were reversed by cinnamaldehyde. The ability of cinnamaldehyde to suppress STAT activation was also verified by the observation that it significantly increased SCOS-3 protein level. These findings indicate for the first time that in the presence of cinnamaldehyde, the suppression of AGE-induced biological responses is probably mediated by inactivating the JAK2-STAT1/STAT3 cascade or activating the NO pathway. |
Databáze: | OpenAIRE |
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