MicroRNA‐210 repression facilitates advanced glycation end‐product (AGE)‐induced cardiac mitochondrial dysfunction and apoptosis via JNK activation
| Autor: | Jian-Sheng Liu, Wei Wen Kuo, Hong-Chen Chen, Shang-Chuan Ng, Catherine R Paul, Kuan Ho Lin, Chih Yang Huang, Ren-You Zeng, V. Vijaya Padma |
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| Rok vydání: | 2021 |
| Předmět: |
Glycation End Products
Advanced chemistry.chemical_classification Reactive oxygen species MAP Kinase Kinase 4 Kinase Apoptosis Cell Biology Mitochondrion medicine.disease Biochemistry Mitochondria Heart Cell Line Rats Cell biology MicroRNAs chemistry.chemical_compound Downregulation and upregulation chemistry Glycation Diabetic cardiomyopathy medicine Animals Advanced glycation end-product Molecular Biology |
| Zdroj: | Journal of Cellular Biochemistry. 122:1873-1885 |
| ISSN: | 1097-4644 0730-2312 |
| Popis: | Hyperglycemia results in the formation of reactive oxygen species which in turn causes advanced glycation end products (AGEs) formation, leading to diabetic cardiomyopathy. Our previous study showed that AGE-induced reactive oxygen species-dependent apoptosis is mediated via protein kinase C delta (PKCδ)-enhanced mitochondrial damage in cardiomyocytes. By using microRNA (miRNA) database, miRNA-210 was predicted to target c-Jun N-terminal kinase (JNK), which were previously identified as downstream of PKCδ in regulating mitochondrial function. Therefore, we hypothesized that miR-210 mediates PKCδ-dependent upregulation of JNK to cause cardiac mitochondrial damage and apoptosis following AGE exposure. AGE-exposed cells showed activated cardiac JNK, PKCδ, and apoptosis, which were reversed by treatment with a JNK inhibitor and PKCδ-KD (deficient kinase). Cardiac miR-210 and mitochondrial function were downregulated following AGE exposure. Furthermore, JNK was upregulated and involved in AGE-induced mitochondrial damage. Interestingly, luciferase activity of the miR-210 mimic plus JNK WT-3'-untranslated region overexpressed group was significantly lower than that of miR-210 mimic plus JNK MT-3'UTR group, indicating that JNK is a target of miR-210. Moreover, JNK activation induced by AGEs was reduced by treatment with the miR-210 mimic and reversed by treatment with the miR-210 inhibitor, indicating the regulatory function of miR-210 in JNK activation following AGE exposure. Additionally, JNK-dependent mitochondrial dysfunction and apoptosis were reversed following treatment with the miR-210 mimic, while the miR-210 inhibitor showed no effect on JNK-induced mitochondrial dysfunction and apoptosis in AGE-exposed cardiac cells. Taken together, our study showed that PKCδ-enhanced JNK-dependent mitochondrial damage is mediated through the reduction of miR-210 in cardiomyocytes following AGE exposure. |
| Databáze: | OpenAIRE |
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