Sustained adenosine exposure causes endothelial mitochondrial dysfunction via equilibrative nucleoside transporters

Pulmonary Circulation
Junsuk KoQing Lu

Abstract

Adenosine is a potent signaling molecule that has paradoxical effects on lung diseases. We have previously demonstrated that sustained adenosine exposure by inhibition of adenosine degradation impairs lung endothelial barrier integrity and causes intrinsic apoptosis through equilibrative nucleoside transporter1/2-mediated intracellular adenosine signaling. In this study, we further demonstrated that sustained adenosine exposure increased mitochondrial reactive oxygen species and reduced mitochondrial respiration via equilibrative nucleoside transporter1/2, but not via adenosine receptor-mediated signaling. We have previously shown that sustained adenosine exposure activates p38 and c-Jun N-terminal kinases in mitochondria. Here, we show that activation of p38 and JNK partially contributed to sustained adenosine-induced mitochondrial reactive oxygen species production. We also found that sustained adenosine exposure promoted mitochondrial fission and increased mitophagy. Finally, mitochondria-targeted antioxidants prevented sustained adenosine exposure-induced mitochondrial fission and improved cell survival. Our results suggest that inhibition of equilibrative nucleoside transporter1/2 and mitochondria-targeted antioxidants may...Continue Reading

References

Jul 1, 1995·Neurobiology of Aging·G Benzi, A Moretti
Nov 24, 1999·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·S D RossI L Kron
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J L ChunnM R Blackburn
May 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·Detlev BoisonHanns Mohler
Aug 4, 2004·British Journal of Pharmacology·Richard G E ArcherJames R Hammond
Sep 25, 2004·American Journal of Respiratory Cell and Molecular Biology·Christelle D DouilletPreston B Rich
Dec 4, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Julia RivoIdit Matot
Apr 6, 2005·Human Molecular Genetics·Clayton L UlreyTrygve O Tollefsbol
Apr 26, 2005·Circulation Journal : Official Journal of the Japanese Circulation Society·Kazunobu IshikawaYukio Maruyama
Dec 17, 2005·Current Opinion in Pulmonary Medicine·Amir Mohsenin, Michael R Blackburn
Jan 10, 2006·American Journal of Respiratory Cell and Molecular Biology·Yao LiJ P Clancy
Mar 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan B VolmerMichael R Blackburn
Jul 15, 2006·The Journal of Clinical Investigation·Chun-Xiao SunMichael R Blackburn
Dec 28, 2006·Hypertension·Eiki Takimoto, David A Kass
Jun 15, 2007·The Journal of Biological Chemistry·Tao ShenRui-Ping Xiao
Sep 29, 2007·Circulation Research·Xiaomei GuoRui-Ping Xiao
Dec 7, 2007·Blood·Tobias EckleHolger K Eltzschig
Mar 1, 2008·Blood·Julio C Morote-GarciaHolger K Eltzschig
Mar 18, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Sergio AlunniLaura Ottavi
Jun 4, 2008·Biochimica Et Biophysica Acta·Gilad TwigOrian S Shirihai
Jun 19, 2008·Genes & Development·Der-Fen SuenRichard J Youle
May 23, 2009·Inhalation Toxicology·G R ThoméM R C Schetinger
Jun 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yang ZhouMichael R Blackburn
Jul 9, 2009·Physiological Reviews·Marc LiesaAntonio Zorzano
Jul 30, 2009·Handbook of Experimental Pharmacology·Michael R BlackburnConstance N Wilson
Sep 8, 2009·Biochimica Et Biophysica Acta·Konstanze F Winklhofer, Christian Haass
Sep 16, 2009·The Journal of Cell Biology·Junko WakabayashiHiromi Sesaki
Mar 17, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Qing LuSharon Rounds
May 25, 2010·Immunology and Allergy Clinics of North America·H Bobby Gaspar
Aug 26, 2010·British Journal of Pharmacology·T TakahashiS Ito
Oct 5, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Kathleen A StringerTheodore J Standiford
Dec 7, 2010·Free Radical Biology & Medicine·Magali Dumont, M Flint Beal
Dec 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yang ZhouMichael R Blackburn
Mar 14, 2012·Trends in Biochemical Sciences·Fabian FischerHeinz D Osiewacz
Jun 30, 2012·American Journal of Respiratory Cell and Molecular Biology·Qing LuMesias Pedroza
Sep 1, 2012·Annual Review of Genetics·David C Chan

❮ Previous
Next ❯

Citations

Dec 22, 2020·BioMed Research International·Safaa M NaesAmirah Abdul Rahman

❮ Previous
Next ❯

Methods Mentioned

BETA
bronchoalveolar
lavage
PAECs
protein assay
fluorescence microscopy
inverted microscopy

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.