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AntagomiR-451 inhibits oxygen glucose deprivation (OGD)-induced HUVEC necrosis via activating AMPK signaling
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 4, p e0175507 (2017)
- Publication Year :
- 2017
-
Abstract
- Oxygen glucose deprivation (OGD) application in cultured human umbilical vein endothelial cells (HUVECs) mimics ischemic injuries. AntagomiR-451, the miroRNA-451 ("miR-451") inhibitor, could activate pro-survival AMP-activated protein kinase (AMPK) signaling. In the current study, we showed that forced-expression of antagomiR-451 depleted miRNA-451 and significantly attenuated OGD-induced necrosis of HUVECs. Activation of AMPK was required for antagomiR-451-mediated pro-survival actions. AMPK inhibition, by AMPKα shRNA or dominant negative mutation, almost completely abolishedantagomiR-451-mediated HUVEC protection again OGD. Reversely, forced-activation of AMPK by exogenous expression of constructively-active AMPKα inhibited OGD-induced HUVEC necrosis. At the molecular level, antagomiR-451 expression in HUVECs inhibited OGD-induced programmed necrosis, the latter was evidenced by mitochondrial p53-cyclophilinD (Cyp-D) association, mitochondrial depolarization as well as reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) breach. Together, we suggest that antagomiR-451 activates AMPK to inhibit OGD-induced programmed necrosis in HUVECs.
- Subjects :
- 0301 basic medicine
Necrosis
Physiology
lcsh:Medicine
Apoptosis
Mitochondrion
AMP-Activated Protein Kinases
Pathology and Laboratory Medicine
Biochemistry
Umbilical vein
Cyclophilins
Cell Signaling
Medicine and Health Sciences
Enzyme assays
Colorimetric assays
RNA, Small Interfering
lcsh:Science
Bioassays and physiological analysis
Energy-Producing Organelles
chemistry.chemical_classification
Multidisciplinary
MTT assay
Cell Death
Chemistry
Cell biology
Mitochondria
Electrophysiology
Cell Processes
RNA Interference
Signal transduction
medicine.symptom
Cellular Structures and Organelles
Cyclophilin D
Signal Transduction
Research Article
Signal Inhibition
Cell Survival
Bioenergetics
Glucose Signaling
Membrane Potential
Necrotic Cell Death
03 medical and health sciences
Signs and Symptoms
Diagnostic Medicine
medicine
Human Umbilical Vein Endothelial Cells
Humans
Protein kinase A
Reactive oxygen species
lcsh:R
AMPK
Antagomirs
Biology and Life Sciences
Cell Biology
carbohydrates (lipids)
Oxygen
Research and analysis methods
MicroRNAs
030104 developmental biology
Glucose
nervous system
Biochemical analysis
lcsh:Q
Depolarization
Tumor Suppressor Protein p53
Reactive Oxygen Species
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....546dbb8f12812ef2c995aeadb8ad395d