Oxidized LDL Disrupts Metabolism and Inhibits Macrophage Survival by Activating a miR-9/Drp1/Mitochondrial Fission Signaling Pathway.

Oxidative Medicine and Cellular Longevity
Ting XinJin Zhang

Abstract

Mitochondrial dysfunction is associated with macrophage damage, but the role of mitochondrial fission in macrophage cholesterol metabolism is not fully understood. In this study, we explored the influences of miR-9 and mitochondrial fission on macrophage viability and cholesterol metabolism. Macrophages were incubated with oxidized low-density lipoprotein (ox-LDL) in vitro, after which mitochondrial fission, cell viability, and cholesterol metabolism were examined using qPCR, ELISAs, and immunofluorescence. ox-LDL treatment significantly increased Drp1-associated mitochondrial fission. Transfection of Drp1 siRNA significantly reduced cell death, attenuated oxidative stress, and inhibited inflammatory responses in ox-LDL-treated macrophages. Interestingly, inhibition of Drp1-related mitochondrial fission also improved cholesterol metabolism by balancing the transcription of cholesterol influx/efflux enzymes. We also found that miR-9 was downregulated in ox-LDL-treated macrophages, and administration of a miR-9 mimic decreased Drp1 transcription and mitochondrial fission, as well as its effects. These results indicate that signaling via the novel miR-9/Drp1/mitochondrial fission axis is a key determinant of macrophage viability a...Continue Reading

References

Sep 30, 2015·Free Radical Biology & Medicine·Annette Graham
Oct 24, 2015·Journal of Cellular and Molecular Medicine·Dimitry A ChistiakovAlexander N Orekhov
Jun 12, 2016·Antioxidants & Redox Signaling·John D ShortReto Asmis
Mar 24, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Yue WangChangqian Wang
Mar 28, 2017·Journal of Cellular Physiology·Zahra HoseiniHamed Mirzaei
Aug 9, 2017·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Dimitry A ChistiakovAlexander N Orekhov
Jan 11, 2018·Journal of Cellular Physiology·Abbas Shapouri-MoghaddamAmirhossein Sahebkar
Jan 18, 2018·Basic Research in Cardiology·Nkanyiso HadebeSandrine Lecour
Jul 13, 2018·Frontiers in Physiology·Mark S GibsonOtilia V Vieira
Jul 22, 2018·Cell Death and Differentiation·Anna L AaltoAnnika Meinander
Aug 12, 2018·Journal of Molecular and Cellular Cardiology·Callum J DonaldsonLingfang Zeng
Aug 19, 2018·Basic Research in Cardiology·Hans Erik BøtkerGerd Heusch
Dec 7, 2018·Redox Biology·Jason D MatthewsAndrew S Neish
Dec 5, 2018·Redox Biology·Bernice Woon Li LeeDerrick Sek Tong Ong
Dec 21, 2018·Cell Death and Differentiation·Donna Denton, Sharad Kumar
Dec 24, 2018·Redox Biology·Alicia J Kowaltowski
Dec 24, 2018·Redox Biology·Catarina B Afonso, Corinne M Spickett
May 17, 2019·DNA and Cell Biology·Wenxi PengDangheng Wei
Jun 4, 2019·Basic Research in Cardiology·Sujith DassanayakaSteven P Jones
Jun 8, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jie ZhenYang Liu
Sep 1, 2019·Current Pharmaceutical Design·Eskandar TaghizadehAmirhossein Sahebkar
Nov 7, 2019·Food & Function·Fang-Chun Wu, Jian-Guo Jiang
Nov 14, 2019·Journal of Clinical Medicine·Dimitry A ChistiakovAlexander N Orekhov
Nov 16, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Sai YangZhi-Sheng Jiang
Nov 17, 2019·Trends in Immunology·Valentina Guerrini, Maria Laura Gennaro
Nov 25, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Si-Tong FengYi Zhang
Dec 19, 2019·Journal of Clinical Medicine·Emma L SollyJoanne T M Tan
Dec 19, 2019·Frontiers in Cell and Developmental Biology·Eleanor R SteadIvana Bjedov
Dec 24, 2019·The American Journal of Pathology·Maria G Tinajero, Avrum I Gotlieb

❮ Previous
Next ❯

Citations

Aug 28, 2021·Biomedicines·Nataliya V MushenkovaAlexander N Orekhov

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
ELISA
PCR

Software Mentioned

Prism
GraphPad

Related Concepts

Related Feeds

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.