PDF
Full
Outline
OBJECTIVE Astragaloside Ⅳ (AS-Ⅳ) is one of the main active ingredients of astragaloside, which is widely used in treating cardiovascular diseases. The zinc ion (Zn2+) chelating agent N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) can induce excessive mitochondrial autophagy and lead to myocardial cell injury. This study investigated whether AS-Ⅳ could inhibit mitochondrial autophagy mediated by fun14 domain containing 1 (FUNDC1) induced by zinc deficiency, thereby reducing the damage of H9c2 cardiomyocytes, and exploring the potential intracellular signal transduction mechanism. METHODS H9c2 cardiomyocytes were cultured using routine methods, and a zinc deficiency model was induced by TPEN. The cells were then randomly assigned to the control group, TPEN group, TPEN+AS-Ⅳ group, and AS-Ⅳ group. Cell viability was assessed using the CCK8 method; cytotoxicity was measured with lactate dehydrogenase (LDH) kits. A zinc ion detection kit was utilized to quantify intracellular zinc content. The changes in mitochondrial Zn2+, lysosome and mitochondrial membrane potential were detected by fluorescence microscopy and fluorescence enzyme labeling. The expression levels of autophagy-related proteins microtubule-associated protein 1A/1B light chain 3 (LC3 Ⅱ/Ⅰ), FUNDC1, sequestosome-1 (P62/SQSTM1), and translocase of the outer membrane 20 (TOM20) were detected by Western blot. Immunofluorescence analysis was performed for LC3 and FUNDC1; FUNDC1 siRNA transfection was conducted. RESULTS Compared with the control group, treatment with 10 μmol·L-1 TPEN for 4 h significantly decreased cell viability, increased LDH release, and reduced intracellular zinc content. The red fluorescence intensity of mitochondrial Rhodzin-3 and tetramethylrhodamine ethyl ester perchlorate significantly decreased, while the red fluorescence intensity of lysosomal Lyso Tracker significantly increased. The protein expressions of LC3 and FUNDC1 were markedly elevated, whereas the protein expressions of P62 and TOM20 decreased. The expression of LC3 Ⅱ/Ⅰ and FUNDC1's green fluorescent protein is significantly increased. Pretreatment with 50 μmol·L-1 AS-Ⅳ for 2 h significantly suppressed the aforementioned processes. Silencing FUNDC1 with siRNA further enhanced AS-Ⅳ's inhibitory effect on autophagy, with statistically significant differences (P<0.05). CONCLUSION By increasing Zn2+ in H9c2 cells, AS-Ⅳ can inhibit TPEN-induced mitochondrial hyperautophagy mediated by FUNDC1 and inhibit the opening of mPTP, thus playing a myocardial protective role.
PDF
226
97
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
关闭全屏
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
