HIF-1α Preconditioning Potentiates Antioxidant Activity in Ischemic Injury: The Role of Sequential Administration of Dihydrotanshinone I and Protocatechuic Aldehyde in Cardioprotection.

Antioxidants & Redox Signaling
Lifeng JiangPing Li

Abstract

Aims: The management of myocardial ischemia has been challenged by reperfusion injury. Reactive oxygen species (ROS) production is the critical cause of reperfusion injury, but antioxidant treatment failed to gain satisfactory effects. We hypothesized that improvement of redox homeostasis by preconditioning regulation should potentiate the ability of antioxidants to protect the heart from reperfusion injury. Results: By phenotype-based screening, we identified that dihydrotanshinone I (DT) and protocatechuic aldehyde (PCA) potently protected cardiomyocytes through preconditioning regulation and antioxidant activity, respectively. DT induced transient ROS generation via reversible inhibition of mitochondrial respiratory complex I and thereby stabilizing HIF-1α, while PCA elevated the levels of reduced glutathione (GSH) by providing reducing equivalents to scavenge ROS. HIF-1α, stabilized by DT, transcriptionally upregulated Nrf2 and thereby activated antioxidant enzymes, potentiating PCA to protect cardiomyocytes from reperfusion injury by strengthening intrinsic ROS scavenging capacity. In rat ischemia/reperfusion (I/R) model, sequential administration of DT and PCA, but not in reverse, additively protected the heart from I/R i...Continue Reading

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Citations

Jun 18, 2021·Vascular Health and Risk Management·Robert T MalletMartin Burtscher
Aug 17, 2021·Phytotherapy Research : PTR·Muhammad Ajmal ShahGaber El-Saber Batiha

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Methods Mentioned

BETA
PCA
confocal microscopy
nuclear translocation
ELISA
enzyme-linked immunosorbent assay
RNA-Seq
PCR
Assay
transfection
Protein Assay

Software Mentioned

Image Pro Plus (
GraphPad Prism
Prism
ImageJ

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