Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes
Brain-derived neurotrophic factor (BDNF) has recently been recognized as a cardiovascular regulator particularly in the diseased condition, including coronary artery disease, heart failure, cardiomyopathy, and hypertension. Here, we investigate the role of BDNF on the T-type Ca<sup>2+</sup&...
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MDPI AG
2021-06-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/11/7/470 |
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| author | Masaki Morishima Takafumi Fujita Satoshi Osagawa Hiroshi Kubota Katsushige Ono |
| author_facet | Masaki Morishima Takafumi Fujita Satoshi Osagawa Hiroshi Kubota Katsushige Ono |
| author_sort | Masaki Morishima |
| collection | DOAJ |
| description | Brain-derived neurotrophic factor (BDNF) has recently been recognized as a cardiovascular regulator particularly in the diseased condition, including coronary artery disease, heart failure, cardiomyopathy, and hypertension. Here, we investigate the role of BDNF on the T-type Ca<sup>2+</sup> channel, Cav3.1 and Cav3.2, in rat neonatal cardiomyocytes exposed to normoxia (21% O<sub>2</sub>) and acute hypoxia (1% O<sub>2</sub>) in vitro for up to 3 h. The exposure of cardiomyocytes to hypoxia (1 h, 3 h) caused a significant upregulation of the mRNAs for hypoxia-inducible factor 1α (<i>H</i><i>if1</i><i>α</i>), <i>Cav3.1</i>, <i>Cav3.2</i> and <i>B</i><i>dnf</i>, but not tropomyosin-related kinase receptor B (<i>TrkB</i>). The upregulation of <i>Cav3.1</i> and <i>Cav3.2</i> caused by hypoxia was completely halted by small interfering RNA (siRNA) targeting <i>H</i><i>if1</i><i>a</i> (<i>H</i><i>if1</i><i>a</i>-siRNA) or <i>B</i><i>dnf</i> (<i>B</i><i>dnf</i>-siRNA). Immunocytochemical staining data revealed a distinct upregulation of Cav3.1- and Cav3.2-proteins caused by hypoxia in cardiomyocytes, which was markedly suppressed by <i>B</i><i>dnf</i>-siRNA. These results unveiled a novel regulatory action of BDNF on the T-type Ca<sup>2+</sup> channels expression through the HIF-1α-dependent pathway in cardiomyocytes. |
| first_indexed | 2024-03-10T10:03:46Z |
| format | Article |
| id | doaj.art-9bfdaa79ab7d4765aa93d3aa9bb29c44 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T10:03:46Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-9bfdaa79ab7d4765aa93d3aa9bb29c442023-11-22T01:45:16ZengMDPI AGMembranes2077-03752021-06-0111747010.3390/membranes11070470Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat CardiomyocytesMasaki Morishima0Takafumi Fujita1Satoshi Osagawa2Hiroshi Kubota3Katsushige Ono4Department of Food and Nutrition, Kindai University Faculty of Agriculture, Nara 631-8505, JapanDepartment of Pathophysiology, Oita University School of Medicine, Oita 879-5593, JapanDepartment of Pathophysiology, Oita University School of Medicine, Oita 879-5593, JapanDepartment of Pathophysiology, Oita University School of Medicine, Oita 879-5593, JapanDepartment of Pathophysiology, Oita University School of Medicine, Oita 879-5593, JapanBrain-derived neurotrophic factor (BDNF) has recently been recognized as a cardiovascular regulator particularly in the diseased condition, including coronary artery disease, heart failure, cardiomyopathy, and hypertension. Here, we investigate the role of BDNF on the T-type Ca<sup>2+</sup> channel, Cav3.1 and Cav3.2, in rat neonatal cardiomyocytes exposed to normoxia (21% O<sub>2</sub>) and acute hypoxia (1% O<sub>2</sub>) in vitro for up to 3 h. The exposure of cardiomyocytes to hypoxia (1 h, 3 h) caused a significant upregulation of the mRNAs for hypoxia-inducible factor 1α (<i>H</i><i>if1</i><i>α</i>), <i>Cav3.1</i>, <i>Cav3.2</i> and <i>B</i><i>dnf</i>, but not tropomyosin-related kinase receptor B (<i>TrkB</i>). The upregulation of <i>Cav3.1</i> and <i>Cav3.2</i> caused by hypoxia was completely halted by small interfering RNA (siRNA) targeting <i>H</i><i>if1</i><i>a</i> (<i>H</i><i>if1</i><i>a</i>-siRNA) or <i>B</i><i>dnf</i> (<i>B</i><i>dnf</i>-siRNA). Immunocytochemical staining data revealed a distinct upregulation of Cav3.1- and Cav3.2-proteins caused by hypoxia in cardiomyocytes, which was markedly suppressed by <i>B</i><i>dnf</i>-siRNA. These results unveiled a novel regulatory action of BDNF on the T-type Ca<sup>2+</sup> channels expression through the HIF-1α-dependent pathway in cardiomyocytes.https://www.mdpi.com/2077-0375/11/7/470BDNFTrkBHIF-1αCav3.1Cav3.2T-type Ca<sup>2+</sup> channel |
| spellingShingle | Masaki Morishima Takafumi Fujita Satoshi Osagawa Hiroshi Kubota Katsushige Ono Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes Membranes BDNF TrkB HIF-1α Cav3.1 Cav3.2 T-type Ca<sup>2+</sup> channel |
| title | Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes |
| title_full | Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes |
| title_fullStr | Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes |
| title_full_unstemmed | Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes |
| title_short | Enhanced BDNF Actions Following Acute Hypoxia Facilitate HIF-1α-Dependent Upregulation of Cav3-T-Type Ca<sup>2+</sup> Channels in Rat Cardiomyocytes |
| title_sort | enhanced bdnf actions following acute hypoxia facilitate hif 1α dependent upregulation of cav3 t type ca sup 2 sup channels in rat cardiomyocytes |
| topic | BDNF TrkB HIF-1α Cav3.1 Cav3.2 T-type Ca<sup>2+</sup> channel |
| url | https://www.mdpi.com/2077-0375/11/7/470 |
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