Exposure to 15% oxygen in vivo up-regulates cardioprotective SUR2A without affecting ERK1/2 and AKT: a crucial role for AMPK

Khaja Shameem Mohammed Abdul, Sofija Jovanovic, Aleksandar Jovanovic (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Abstract

SUR2A is an “atypical” ABC protein that forms sarcolemmal ATP-sensitive K+ (KATP) channels by binding to inward rectifier Kir6.2. Manipulation with SUR2A levels have been suggested to be a promising therapeutic strategy against ischaemic heart diseases and other diseases where increased heart resistance to stress is beneficial. Some years ago, it has been reported that high-altitude residents have lower mortality rates for ischaemic heart disease. The purpose of this study was to determine whether SUR2A is regulated by mild to severe hypoxic conditions (15% oxygen; oxygen tension equivalent to 3000 m above sea level) and elucidate the underlying mechanism. Mice were exposed to either to 21% (control) or 15% concentration of oxygen for 24h. 24h-long exposure to 15% oxygen decreased partial pressure of O2 (PO2), but did not affect blood CO2 (PCO2), haematocrit nor levels of ATP, lactate and NAD+/NADH in the heart. Cardiac SUR2A levels were significantly increased while Kir6.2 levels were not affected. Hypoxia did not induce phosphorylation of extracellular signal regulated kinases (ERK1/2) or protein kinase B (Akt), but triggered phosphorylation of AMP activated protein kinase (AMPK). AICAR, an activator of AMPK, increased the level of SUR2A in H9c2 cells. We conclude that oxygen increases SUR2A level by activating AMPK. This is the first account of AMPK-mediated regulation of SUR2A.
Original languageEnglish
Pages (from-to)1342-1350
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume21
Issue number7
Early online date25 Jan 2017
DOIs
Publication statusPublished - Jul 2017

Keywords

  • Hypoxia
  • Oxygen
  • SUR2A
  • Heart
  • AMPK

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