A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
Summary: Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte; its inhibitory activity to sarcolemma-endoplasmic reticulum calcium ATPase is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in the failing heart. The current study pro...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | JACC: Basic to Translational Science |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X17300505 |
| _version_ | 1818024677129322496 |
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| author | Toru Akaike, MD, PhD Na Du, MD, PhD Gang Lu, PhD Susumu Minamisawa, MD, PhD Yibin Wang, PhD Hongmei Ruan, MD, PhD |
| author_facet | Toru Akaike, MD, PhD Na Du, MD, PhD Gang Lu, PhD Susumu Minamisawa, MD, PhD Yibin Wang, PhD Hongmei Ruan, MD, PhD |
| author_sort | Toru Akaike, MD, PhD |
| collection | DOAJ |
| description | Summary: Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte; its inhibitory activity to sarcolemma-endoplasmic reticulum calcium ATPase is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in the failing heart. The current study provided evidence at the molecular, cellular, and whole-heart levels to implicate a sarcolemma membrane-targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β-adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis. Key Words: heart, phosphatase, phospholamban |
| first_indexed | 2024-12-10T04:04:01Z |
| format | Article |
| id | doaj.art-60c8611e611e40c891e848de973f9857 |
| institution | Directory Open Access Journal |
| issn | 2452-302X |
| language | English |
| last_indexed | 2024-12-10T04:04:01Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JACC: Basic to Translational Science |
| spelling | doaj.art-60c8611e611e40c891e848de973f98572022-12-22T02:02:53ZengElsevierJACC: Basic to Translational Science2452-302X2017-04-0122160180A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the HeartToru Akaike, MD, PhD0Na Du, MD, PhD1Gang Lu, PhD2Susumu Minamisawa, MD, PhD3Yibin Wang, PhD4Hongmei Ruan, MD, PhD5Department of Anesthesiology and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California; Department of Cell Physiology, The Jikei University School of Medicine, Tokyo, JapanDepartment of Anesthesiology and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CaliforniaDepartment of Anesthesiology and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CaliforniaDepartment of Cell Physiology, The Jikei University School of Medicine, Tokyo, JapanDepartment of Anesthesiology and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California; Address for correspondence: Dr. Yibin Wang OR Dr. Hongmei Ruan, Cardiovascular Research Laboratories at UCLA, Department of Anesthesiology, Charles E. Young Drive South, 650, Los Angeles, California 90095.Department of Anesthesiology and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California; Address for correspondence: Dr. Yibin Wang OR Dr. Hongmei Ruan, Cardiovascular Research Laboratories at UCLA, Department of Anesthesiology, Charles E. Young Drive South, 650, Los Angeles, California 90095.Summary: Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte; its inhibitory activity to sarcolemma-endoplasmic reticulum calcium ATPase is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in the failing heart. The current study provided evidence at the molecular, cellular, and whole-heart levels to implicate a sarcolemma membrane-targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β-adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis. Key Words: heart, phosphatase, phospholambanhttp://www.sciencedirect.com/science/article/pii/S2452302X17300505 |
| spellingShingle | Toru Akaike, MD, PhD Na Du, MD, PhD Gang Lu, PhD Susumu Minamisawa, MD, PhD Yibin Wang, PhD Hongmei Ruan, MD, PhD A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart JACC: Basic to Translational Science |
| title | A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart |
| title_full | A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart |
| title_fullStr | A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart |
| title_full_unstemmed | A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart |
| title_short | A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart |
| title_sort | sarcoplasmic reticulum localized protein phosphatase regulates phospholamban phosphorylation anda promotes ischemia reperfusion injurya ina the heart |
| url | http://www.sciencedirect.com/science/article/pii/S2452302X17300505 |
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