Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress
Myocardial ischemia-reperfusion injury (I/R) causes damage to cardiomyocytes through oxidative stress and apoptosis. We investigated the cardioprotective effects of MnTnBuOE-2-PyP<sup>5+</sup> (BMX-001), a superoxide dismutase mimic, in an in vitro model of I/R injury in H9c2 cardiomyocy...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6159 |
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| author | Sudha Sharma Papori Sharma Utsab Subedi Susmita Bhattarai Chloe Miller Shrivats Manikandan Ines Batinic-Haberle Ivan Spasojevic Hong Sun Manikandan Panchatcharam Sumitra Miriyala |
| author_facet | Sudha Sharma Papori Sharma Utsab Subedi Susmita Bhattarai Chloe Miller Shrivats Manikandan Ines Batinic-Haberle Ivan Spasojevic Hong Sun Manikandan Panchatcharam Sumitra Miriyala |
| author_sort | Sudha Sharma |
| collection | DOAJ |
| description | Myocardial ischemia-reperfusion injury (I/R) causes damage to cardiomyocytes through oxidative stress and apoptosis. We investigated the cardioprotective effects of MnTnBuOE-2-PyP<sup>5+</sup> (BMX-001), a superoxide dismutase mimic, in an in vitro model of I/R injury in H9c2 cardiomyocytes. We found that BMX-001 protected against hypoxia/reoxygenation (H/R)-induced oxidative stress, as evident by a significant reduction in intracellular and mitochondrial superoxide levels. BMX-001 pre-treatment also reduced H/R-induced cardiomyocyte apoptosis, as marked by a reduction in TUNEL-positive cells. We further demonstrated that BMX-001 pre-treatment significantly improved mitochondrial function, particularly O<sub>2</sub> consumption, in mouse adult cardiomyocytes subjected to H/R. BMX-001 treatment also attenuated cardiolipin peroxidation, 4-hydroxynonenal (4-HNE) level, and 4-HNE adducted proteins following H/R injury. Finally, the pre-treatment with BMX-001 improved cell viability and lactate dehydrogenase (LDH) activity in H9c2 cells following H/R injury. Our findings suggest that BMX-001 has therapeutic potential as a cardioprotective agent against oxidative stress-induced H/R damage in H9c2 cardiomyocytes. |
| first_indexed | 2024-03-11T05:36:09Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:09Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bdc62df0428144ceb5c2810a61b9c6812023-11-17T16:47:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247615910.3390/ijms24076159Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative StressSudha Sharma0Papori Sharma1Utsab Subedi2Susmita Bhattarai3Chloe Miller4Shrivats Manikandan5Ines Batinic-Haberle6Ivan Spasojevic7Hong Sun8Manikandan Panchatcharam9Sumitra Miriyala10Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Radiation Oncology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Medicine, Duke University School of Medicine, Durham, NC 27710, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USADepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences-Shreveport, Shreveport, LA 71103, USAMyocardial ischemia-reperfusion injury (I/R) causes damage to cardiomyocytes through oxidative stress and apoptosis. We investigated the cardioprotective effects of MnTnBuOE-2-PyP<sup>5+</sup> (BMX-001), a superoxide dismutase mimic, in an in vitro model of I/R injury in H9c2 cardiomyocytes. We found that BMX-001 protected against hypoxia/reoxygenation (H/R)-induced oxidative stress, as evident by a significant reduction in intracellular and mitochondrial superoxide levels. BMX-001 pre-treatment also reduced H/R-induced cardiomyocyte apoptosis, as marked by a reduction in TUNEL-positive cells. We further demonstrated that BMX-001 pre-treatment significantly improved mitochondrial function, particularly O<sub>2</sub> consumption, in mouse adult cardiomyocytes subjected to H/R. BMX-001 treatment also attenuated cardiolipin peroxidation, 4-hydroxynonenal (4-HNE) level, and 4-HNE adducted proteins following H/R injury. Finally, the pre-treatment with BMX-001 improved cell viability and lactate dehydrogenase (LDH) activity in H9c2 cells following H/R injury. Our findings suggest that BMX-001 has therapeutic potential as a cardioprotective agent against oxidative stress-induced H/R damage in H9c2 cardiomyocytes.https://www.mdpi.com/1422-0067/24/7/6159superoxidecardiomyocytesSOD2apoptosis |
| spellingShingle | Sudha Sharma Papori Sharma Utsab Subedi Susmita Bhattarai Chloe Miller Shrivats Manikandan Ines Batinic-Haberle Ivan Spasojevic Hong Sun Manikandan Panchatcharam Sumitra Miriyala Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress International Journal of Molecular Sciences superoxide cardiomyocytes SOD2 apoptosis |
| title | Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress |
| title_full | Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress |
| title_fullStr | Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress |
| title_full_unstemmed | Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress |
| title_short | Mn(III) Porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress |
| title_sort | mn iii porphyrin mntnbuoe 2 pyp sup 5 sup commonly known as a mimic of superoxide dismutase enzyme protects cardiomyocytes from hypoxia reoxygenation induced injury via reducing oxidative stress |
| topic | superoxide cardiomyocytes SOD2 apoptosis |
| url | https://www.mdpi.com/1422-0067/24/7/6159 |
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