Luteolin modulates SERCA2a via Sp1 upregulation to attenuate myocardial ischemia/reperfusion injury in mice.

Abstract

The sarco/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) is responsible for calcium transport during excitation-contraction coupling and is essential for maintaining myocardial systolic/diastolic function and intracellular Ca2+ levels. Therefore, it is important to investigate mechanisms whereby luteolin modulates SERCA2a expression to attenuate myocardial ischemia/reperfusion injury. C57BL/6j mice were randomly divided into eight groups. The expression and activity of SERCA2a was measured to assess interactions between the SERCA2a promoter and the Sp1 transcription factor, and the regulatory effects of luteolin. We used serum LDH release, serum cardiac troponin I level, hemodynamic data, myocardial infarction size and apoptosis-related indices to measure SERCA2a cardio-protective effects of luteolin pretreatment. Sp1 binding to SERCA2a promoter under ischemia/reperfusion conditions in the presence or absence of luteolin was analyzed by chromatin immunoprecipitation. Our experimental results indicated that during myocardial ischemia/reperfusion injury, luteolin pretreatment upregulated the expression levels of SERCA2a and Sp1. Sp1 overexpression enhanced the expression of SERCA2a at the transcriptional level. Luteolin pretreatment reversed the expression of SERCA2a through the increased expression of Sp1. Moreover, we demonstrated that luteolin pretreatment appeared to exert myocardial protective effects by upregulating the transcriptional activity of SERCA2a, via Sp1. In conclusion, during myocardial ischemia/reperfusion, Sp1 appeared to downregulate the expression of SERCA2a. Luteolin pretreatment was shown to improve SERCA2a expression via the upregulation of Sp1 to attenuate myocardial ischemia/reperfusion injury.

• Authors: Ya Hu, Chengmeng Zhang, Hong Zhu, Shuai Wang, Yao Zhou, Jiaqi Zhao, Yong Xia, Dongye Li
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 15407 (09 21 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32958799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sp1 Transcription Factor
• Sarcoplasmic Reticulum Calcium-Transporting ATPases
• Atp2a2 protein, mouse
• Luteolin

Topics

• Animals
• Luteolin (metabolism, pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (metabolism)
• Myocardial Ischemia (drug therapy, metabolism)
• Myocardial Reperfusion Injury (metabolism)
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Reperfusion Injury (drug therapy)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (genetics, metabolism)
• Sp1 Transcription Factor (metabolism, physiology)