Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel β1 subunit degradation in diabetic mice.

Diabetes
Tong LuHon-Chi Lee

Abstract

Activity of the vascular large conductance Ca(2+)-activated K(+) (BK) channel is tightly regulated by its accessory β(1) subunit (BK-β(1)). Downregulation of BK-β(1) expression in diabetic vessels is associated with upregulation of the forkhead box O subfamily transcription factor-3a (FOXO-3a)-dependent F-box-only protein (FBXO) expression. However, the upstream signaling regulating this process is unclear. Overproduction of reactive oxygen species (ROS) is a common finding in diabetic vasculopathy. We hypothesized that ROS signaling cascade facilitates the FOXO-3a/FBXO-mediated BK-β(1) degradation and leads to diabetic BK channel dysfunction. Using cellular biology, patch clamp, and videomicroscopy techniques, we found that reduced BK-β(1) expression in streptozotocin (STZ)-induced diabetic mouse arteries and in human coronary smooth muscle cells (SMCs) cultured with high glucose was attributable to an increase in protein kinase C (PKC)-β and NADPH oxidase expressions and accompanied by attenuation of Akt phosphorylation and augmentation of atrogin-1 expression. Treatment with ruboxistaurin (a PKCβ inhibitor) or with GW501516 (a peroxisome proliferator-activated receptor δ activator) reduced atrogin-1 expression and restored B...Continue Reading

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Citations

Sep 15, 2014·Cell Calcium·María Fernández-VelascoAngélica Rueda
May 6, 2014·Pflügers Archiv : European journal of physiology·Qiang ChaiHon-Chi Lee
May 6, 2014·International Journal of Cardiology·Igor V KizubAnatoly I Soloviev
Aug 31, 2016·Applied Physiology, Nutrition, and Metabolism = Physiologie Appliquée, Nutrition Et Métabolisme·Tong LuHon-Chi Lee
Apr 22, 2017·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Yong LiHon-Chi Lee
Sep 20, 2017·The Journal of Biological Chemistry·Tong LuHon-Chi Lee
Dec 19, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Tongrong HeZvonimir S Katusic
Apr 28, 2018·Circulation Research·Steven J ForresterKathy K Griendling
Jan 13, 2019·The Journal of Biological Chemistry·Tian-You LingHon-Chi Lee
Nov 8, 2018·The Journal of Endocrinology·Gen ChenLitai Jin
Dec 6, 2018·International Journal of Molecular Sciences·Anuradha Tarafdar, Giordano Pula
Jul 1, 2020·Cellular and Molecular Life Sciences : CMLS·Madeline Nieves-CintrónManuel F Navedo
Jun 18, 2020·Frontiers in Physiology·Ling-Ling QianRu-Xing Wang
Dec 1, 2018·Environmental Science and Pollution Research International·Dalia H SamakMohamed M Abdel-Daim
Jan 16, 2021·American Journal of Physiology. Heart and Circulatory Physiology·M Dennis LeoJonathan H Jaggar
Feb 17, 2018·Biochemical Pharmacology·Zhongwei Liu, Raouf A Khalil
Jan 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Xiao-Li WangHon-Chi Lee
Jun 25, 2021·Acta Pharmacologica Sinica·Feng-Ling NingXue-Mei Zhang

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Methods Mentioned

BETA
ubiquitination
fluorescence microscopy

Software Mentioned

SigmaStat
Clampfit
Scion Image

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