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Glucose-sensing microRNA-21 disrupts ROS homeostasis and impairs antioxidant responses in cellular glucose variability

Overview of attention for article published in Cardiovascular Diabetology, July 2018
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Title
Glucose-sensing microRNA-21 disrupts ROS homeostasis and impairs antioxidant responses in cellular glucose variability
Published in
Cardiovascular Diabetology, July 2018
DOI 10.1186/s12933-018-0748-2
Pubmed ID
Authors

Lucia La Sala, Simona Mrakic-Sposta, Stefano Micheloni, Francesco Prattichizzo, Antonio Ceriello

Abstract

Antioxidant enzymes play a fundamental role in counteracting oxidative stress induced by high glucose. Although mitochondrial superoxide dismutase (SOD2) is the principal defence against the toxicity of superoxide anions, the mechanism of its inactivation in diabetic subjects is still poorly understood. Recently, microRNA-21 has been associated with diabetes, although its function remains unclear. We sought to explore the mechanism underlying defective SOD2 antioxidant response in HUVECs during exposures to constant high glucose and oscillating glucose (as glucose variability model, GV) and the role of miR-21 in increasing the susceptibility to oxidative stress by disrupting reactive oxygen species (ROS) homeostasis. HUVECs exposed for 1 week to constant high glucose and GV were subjected to quantitative electron paramagnetic resonance for ROS measurements. Superoxide anions, SOD2 protein levels and mitochondrial membrane potential (ΔΨm) were also evaluated. Endogenous miR-21 and its putative ROS-homeostatic target genes (KRIT1, FoxO1, NFE2L2 and SOD2) were tested using mimic-miR-21 and quantified by qPCR. Luciferase assays were performed to test miR-21/3'-UTR-SOD2 binding. We observed upregulation of microRNA-21, overproduction of superoxide anions and total ROS generation, depolarisation of the mitochondrial membrane potential (ΔΨm) and defective SOD2 antioxidant response in HUVECs subjected to constant high glucose and GV exposures. We also found that exogenous mimic-microRNA-21 targeted putative microRNA-21 ROS-homeostatic target genes, e.g., KRIT1, NRF2 and SOD2, which were significantly downregulated. All these effects were reverted by a microRNA-21 inhibitor, which improved SOD2 and KRIT1 expression, reduced the levels of ROS production and ameliorated ΔΨm. Our data demonstrate the association of microRNA-21 with oscillating and high glucose and early mitochondrial dysfunction. We found that microRNA-21 may promote the suppression of homeostatic signalling that normally limits ROS damage. These data provide novel clues about the inhibition of microRNA-21 as a new therapeutic approach to protect against cellular oxidative injury in glucose variability and diabetes.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 19%
Student > Ph. D. Student 3 14%
Student > Doctoral Student 2 10%
Student > Master 2 10%
Student > Bachelor 1 5%
Other 1 5%
Unknown 8 38%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 4 19%
Medicine and Dentistry 3 14%
Agricultural and Biological Sciences 1 5%
Immunology and Microbiology 1 5%
Nursing and Health Professions 1 5%
Other 1 5%
Unknown 10 48%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 January 2019.
All research outputs
#12,559,082
of 14,207,392 outputs
Outputs from Cardiovascular Diabetology
#686
of 817 outputs
Outputs of similar age
#235,798
of 274,523 outputs
Outputs of similar age from Cardiovascular Diabetology
#1
of 1 outputs
Altmetric has tracked 14,207,392 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 817 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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