The benzodiazepine anesthetic midazolam prevents hyperglycemia-induced microvascular leakage in the retinas of diabetic mice

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Yeon-Ju LeeKwon-Soo Ha

Abstract

We investigated the beneficial effects of midazolam against vascular endothelial growth factor (VEGF)-induced vascular leakage and its molecular mechanism of action in human retinal endothelial cells (HRECs) and the retinas of diabetic mice. Midazolam inhibited VEGF-induced elevation of intracellular Ca2+, generation of reactive oxygen species (ROS), and transglutaminase activation in HRECs; these effects were reversed by the GABA, type A (GABAA) receptor antagonist flumazenil but not by the translocator protein antagonist PK11195. Midazolam also prevented VEGF-induced disassembly of adherens junctions and in vitro permeability. Intravitreal injection of midazolam prevented hyperglycemia-induced ROS generation, transglutaminase activation, and subsequent vascular leakage in the retinas of diabetic mice, and those effects were reversed by flumazenil. The roles of flumazenil were further supported by identifying GABAA receptors in mouse retinas. Thus, midazolam prevents hyperglycemia-induced vascular leakage by inhibiting VEGF-induced intracellular events in the retinas of diabetic mice.-Lee, Y.-J., Kim, M., Lee, J.-Y., Jung, S.-H., Jeon, H.-Y., Lee, S.-A., Kang, S., Han, E.-T., Park, W. S., Hong, S.-H., Kim, Y.-M., Ha, K.-S. The...Continue Reading

References

Mar 30, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A F SteinlaufR J Groszmann
Dec 26, 2001·The Journal of Pharmacology and Experimental Therapeutics·H MöhlerU Rudolph
Aug 7, 2002·European Journal of Pharmacology·Liliana A MonasteroloM Mónica Elías
Dec 4, 2003·Diabetes/metabolism Research and Reviews·Ruth B CaldwellR William Caldwell
Jan 2, 2004·The New England Journal of Medicine·Robert N Frank
May 27, 2005·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·H-P Hammes
Jan 5, 2008·Handbook of Experimental Pharmacology·K T Olkkola, J Ahonen
Jul 18, 2008·Anesthesia and Analgesia·Jan F A HendrickxSteven L Shafer
Mar 20, 2010·Cardiovascular Research·Volker SpindlerJens Waschke
Feb 15, 2012·Ophthalmology·Quan Dong NguyenUNKNOWN RISE and RIDE Research Group
Jan 11, 2013·Physiological Reviews·Josephine M Forbes, Mark E Cooper
Oct 22, 2013·Cardiovascular Research·Young-Cheol LimKwon-Soo Ha
Sep 23, 2014·Cardiovascular Research·Mahendra Prasad BhattKwon-Soo Ha
Jan 17, 2015·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Li LiuGuonian Wang
Oct 16, 2015·British Journal of Clinical Pharmacology·Marco L A Sivilotti
Apr 14, 2016·Biochemistry·Fei LiShelagh Ferguson-Miller
Jul 2, 2016·Expert Opinion on Investigational Drugs·Michael Steven TolentinoMichael John Tolentino
Sep 13, 2016·International Journal of Molecular Sciences·Mark T Bolinger, David A Antonetti
Sep 15, 2016·World Journal of Diabetes·Michael W Stewart
Jul 29, 2017·The Journal of Endocrinology·Yeon-Ju LeeKwon-Soo Ha

❮ Previous
Next ❯

Citations

Aug 30, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jee-Yeon LeeKwon-Soo Ha

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.