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Mitochonic acid 5 activates the MAPK–ERK–yap signaling pathways to protect mouse microglial BV-2 cells against TNFα-induced apoptosis via increased Bnip3-related mitophagy

Overview of attention for article published in Cellular & Molecular Biology Letters, April 2018
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Title
Mitochonic acid 5 activates the MAPK–ERK–yap signaling pathways to protect mouse microglial BV-2 cells against TNFα-induced apoptosis via increased Bnip3-related mitophagy
Published in
Cellular & Molecular Biology Letters, April 2018
DOI 10.1186/s11658-018-0081-5
Pubmed ID
Authors

Qingyun Lei, Jian Tan, Shangqing Yi, Na Wu, Yilin Wang, Heng Wu

Abstract

The regulation of microglial function via mitochondrial homeostasis is important in the development of neuroinflammation. The underlying mechanism for this regulatory function remains unclear. In this study, we investigated the protective role of mitochonic acid 5 (MA-5) in microglial mitochondrial apoptosis following TNFα-induced inflammatory injury. TNFα was used to induce inflammatory injury in mouse microglial BV-2 cells with and without prior MA-5 treatment. Cellular apoptosis was assessed using the MTT and TUNEL assays. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment, and immunofluorescence of cyt-c. Mitophagy was examined using western blots and immunofluorescence. The pathways analysis was carried out using western blots and immunofluorescence with a pathway blocker. Our results demonstrated that TNFα induced apoptosis in the microglial BV-2 cell line by activating the caspase-9-dependent mitochondrial apoptotic pathway. Mechanistically, inflammation reduced mitochondrial potential, induced ROS production, and contributed to the leakage of mitochondrial pro-apoptotic factors into the cytoplasm. The inflammatory response reduced cellular energy metabolism and increased oxidative stress. By contrast, treatment with MA-5 reduced mitochondrial apoptosis via upregulation of mitophagy. Increased mitophagy degraded damaged mitochondria, disrupting mitochondrial apoptosis, neutralizing ROS overproduction, and improving cellular energy production. We also identified that MA-5 regulated mitophagy via Bnip3 through the MAPK-ERK-Yap signaling pathway. Inhibiting this signaling pathway or knocking down Bnip3 expression prevented MA-5 from having beneficial effects on mitochondrial homeostasis and increased microglial apoptosis. After TNFα-induced inflammatory injury, MA-5 affects microglial mitochondrial homeostasis in a manner mediated via the amplification of protective, Bnip3-related mitophagy, which is mediated via the MAPK-ERK-Yap signaling pathway.

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 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 25%
Student > Ph. D. Student 4 14%
Student > Doctoral Student 3 11%
Researcher 3 11%
Student > Bachelor 2 7%
Other 2 7%
Unknown 7 25%
Readers by discipline Count As %
Neuroscience 6 21%
Biochemistry, Genetics and Molecular Biology 4 14%
Pharmacology, Toxicology and Pharmaceutical Science 3 11%
Immunology and Microbiology 2 7%
Sports and Recreations 1 4%
Other 3 11%
Unknown 9 32%

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 09 April 2018.
All research outputs
#10,210,415
of 12,781,938 outputs
Outputs from Cellular & Molecular Biology Letters
#85
of 194 outputs
Outputs of similar age
#206,988
of 274,156 outputs
Outputs of similar age from Cellular & Molecular Biology Letters
#1
of 1 outputs
Altmetric has tracked 12,781,938 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 194 research outputs from this source. They receive a mean Attention Score of 2.3. This one is in the 19th percentile – i.e., 19% of its peers scored the same or lower than it.
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