LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation
The development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 infla...
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MDPI AG
2023-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/3/672 |
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| author | Pinyi Liu Xiaoming Dong Chao Dong Guowen Hou Wenyun Liu Xin Jiang Ying Xin |
| author_facet | Pinyi Liu Xiaoming Dong Chao Dong Guowen Hou Wenyun Liu Xin Jiang Ying Xin |
| author_sort | Pinyi Liu |
| collection | DOAJ |
| description | The development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 inflammasome. MHRT is a newly discovered lncRNA exhibiting cardioprotective effects, demonstrated by inhibiting myocardial hypertrophy via Brg1 and myocardial apoptosis via Nrf2 upregulation. However, the underlying mechanism of MHRT remains unclear. We explored the potential protective effects of MHRT against Ang II-induced myocardial oxidative stress and NLRP3-mediated inflammation by targeting Nrf2. Chronic Ang II administration induced NLRP3 inflammasome activation (increased NLRP3, caspase-1 and interleukin-1β expression), oxidative stress (increased 3-nitrotyrosine and 4-hydroxy-2-nonenal), cardiac dysfunction and decreased MHRT and Nrf2 expression. Lentivirus-mediated MHRT overexpression inhibited Ang II (100 nM)-induced oxidative stress and NLRP3 inflammasome activation in AC16 human cardiomyocyte cells. Mechanistically, MHRT overexpression upregulated the expression and function of Nrf2, as determined by the increased transcription of downstream genes <i>HO-1</i> and <i>CAT</i>, subsequently decreasing intracellular ROS accumulation and inhibiting the expression of thioredoxin-interacting protein (NLRP3 activator) and its direct binding to NLRP3. Accordingly, MHRT could protect against Ang II-induced myocardial injury by decreasing oxidative stress and NLRP3 inflammasome activation via Nrf2 activation. |
| first_indexed | 2024-03-11T07:00:24Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T07:00:24Z |
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| series | Antioxidants |
| spelling | doaj.art-4a31b0492cdb424fb564be2947b1e5472023-11-17T09:18:09ZengMDPI AGAntioxidants2076-39212023-03-0112367210.3390/antiox12030672LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 ActivationPinyi Liu0Xiaoming Dong1Chao Dong2Guowen Hou3Wenyun Liu4Xin Jiang5Ying Xin6Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, ChinaKey Laboratory of Pathobiology, Ministry of Education, and College of Basic Medical Science, Jilin University, Changchun 130021, ChinaKey Laboratory of Pathobiology, Ministry of Education, and College of Basic Medical Science, Jilin University, Changchun 130021, ChinaKey Laboratory of Pathobiology, Ministry of Education, and College of Basic Medical Science, Jilin University, Changchun 130021, ChinaKey Laboratory of Pathobiology, Ministry of Education, and College of Basic Medical Science, Jilin University, Changchun 130021, ChinaJilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, ChinaKey Laboratory of Pathobiology, Ministry of Education, and College of Basic Medical Science, Jilin University, Changchun 130021, ChinaThe development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 inflammasome. MHRT is a newly discovered lncRNA exhibiting cardioprotective effects, demonstrated by inhibiting myocardial hypertrophy via Brg1 and myocardial apoptosis via Nrf2 upregulation. However, the underlying mechanism of MHRT remains unclear. We explored the potential protective effects of MHRT against Ang II-induced myocardial oxidative stress and NLRP3-mediated inflammation by targeting Nrf2. Chronic Ang II administration induced NLRP3 inflammasome activation (increased NLRP3, caspase-1 and interleukin-1β expression), oxidative stress (increased 3-nitrotyrosine and 4-hydroxy-2-nonenal), cardiac dysfunction and decreased MHRT and Nrf2 expression. Lentivirus-mediated MHRT overexpression inhibited Ang II (100 nM)-induced oxidative stress and NLRP3 inflammasome activation in AC16 human cardiomyocyte cells. Mechanistically, MHRT overexpression upregulated the expression and function of Nrf2, as determined by the increased transcription of downstream genes <i>HO-1</i> and <i>CAT</i>, subsequently decreasing intracellular ROS accumulation and inhibiting the expression of thioredoxin-interacting protein (NLRP3 activator) and its direct binding to NLRP3. Accordingly, MHRT could protect against Ang II-induced myocardial injury by decreasing oxidative stress and NLRP3 inflammasome activation via Nrf2 activation.https://www.mdpi.com/2076-3921/12/3/672nuclear factor erythroid 2-related factor 2angiotensin IIoxidative stressNLRP3 inflammasomeslong non-coding RNA MHRT |
| spellingShingle | Pinyi Liu Xiaoming Dong Chao Dong Guowen Hou Wenyun Liu Xin Jiang Ying Xin LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation Antioxidants nuclear factor erythroid 2-related factor 2 angiotensin II oxidative stress NLRP3 inflammasomes long non-coding RNA MHRT |
| title | LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation |
| title_full | LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation |
| title_fullStr | LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation |
| title_full_unstemmed | LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation |
| title_short | LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation |
| title_sort | lncrna mhrt prevents angiotensin ii induced myocardial oxidative stress and nlrp3 inflammasome via nrf2 activation |
| topic | nuclear factor erythroid 2-related factor 2 angiotensin II oxidative stress NLRP3 inflammasomes long non-coding RNA MHRT |
| url | https://www.mdpi.com/2076-3921/12/3/672 |
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