2. Academic Validation
  3. Luteoloside pretreatment attenuates anoxia-induced damage in cardiomyocytes by regulating autophagy mediated by 14-3-3η and the AMPKα-mTOR/ULK1 pathway

Luteoloside pretreatment attenuates anoxia-induced damage in cardiomyocytes by regulating autophagy mediated by 14-3-3η and the AMPKα-mTOR/ULK1 pathway

  • Mol Cell Biochem. 2022 Nov 16. doi: 10.1007/s11010-022-04611-0.
Tianhong Hu # 1,  Lin Wen # 2,  Liang Wang # 3,  Yang Qiao 2,  Xie Cheng 2,  Qigui Fan 2,  Songqing Lai 1,  Huan He 4,  Ming He 5 6
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
  • 2 Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, 330006, China.
  • 3 Department of Rehabilitation, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
  • 4 Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, 330006, China. [email protected].
  • 5 Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China. [email protected].
  • 6 Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, 330006, China. [email protected].
  • # Contributed equally.
PMID: 36385689 DOI: 10.1007/s11010-022-04611-0
Abstract

The relation between ischemia and heart failure is well demonstrated, and several studies suggested that realizing the physiological role of Autophagy will be of great importance. Luteoloside (Lut) is one of the main components of Lonicera japonica flos and exhibits antioxidant, anti-inflammatory, and cardioprotective properties. To determine if Lut pretreatment enhanced Autophagy by 14-3-3η expression and the AMPKα-mTOR/ULK1 pathway and protected the neonatal rat cardiomyocytes (NRCMs) against anoxia damage, NRCMs were treated using 20 μM Lut for 36 h, and the anoxia damage model was established using NRCMs. The indexes reflecting the condition of NRCMs, oxidative stress level, and mitochondrial function were evaluated. In addition, the expression and phosphorylation of 14-3-3η and AMPKα/mTOR/ULK1, and Autophagy markers (LC3II, P62) and the abundance of Autophagy lysosomes were detected. Results revealed that Lut pretreatment alleviated anoxia- induced damage in NRCMs, that is, Lut pretreatment could increase cell viability, decrease LDH activity and Apoptosis, suppressed ROS generation and oxidative stress, restored intracellular ATP levels, stabilized MMP levels, and inhibited mPTP opening. Furthermore, Lut pretreatment could enhance Autophagy via upregulating 14-3-3η, LC3II expression and increasing p-AMPKα/AMPKα and p-ULK1/ULK1 level, whereas P62 expression and p-mTOR/mTOR level decreased; the fluorescence intensity of autolysosomes also increased. However, in the NRCMs treated with pAD/14-3-3η RNAi or incubated with 3-MA (an Autophagy Inhibitor), the abovementioned effects of Lut pretreatment were reduced. Taken together, Lut pretreatment could enhance Autophagy by upregulating 14-3-3η expression to influence the AMPKα-mTOR/ ULK1 pathway against anoxia-induced damage in NRCMs.

Keywords

14-3-3η; AMPKα-mTOR/ULK1 pathway; Anoxia damage; Autophagy; Cardiomyocytes; Luteoloside.

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