Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C

Haiyan Tong, Weina Chen, Charles Steenbergen, Elizabeth Murphy

Research output: Contribution to journalArticle

286 Citations (Scopus)

Abstract

The present study is designed to test whether phosphatidylinositol 3-kinase (PI3-kinase) has a role in the signaling pathway in ischemic preconditioning (PC) and whether it is proximal or distal to protein kinase C (PKC). Before 20 minutes of global ischemia, Langendorff-perfused rat hearts were perfused for 20 minutes (control); preconditioned with 4 cycles of 5-minute ischemia and 5-minute reflow (PC); treated with either wortmannin (WM) or LY 294002 (LY), each of which is a PI3-kinase inhibitor, for 5 minutes before and throughout PC; treated with 1,2-dioctanoyl-sn-glycerol (DOG), an activator of PKC for 10 minutes (DOG); treated identically to the DOG group except with WM added 10 minutes before and during perfusion with DOG; or treated with either WM or LY for 25 minutes. Recovery of left ventricular developed pressure (LVDP; percentage of initial preischemic LVDP), measured after 30 minutes of reflow, was improved by PC (72±2% versus 36±4% in control; P<0.001), and this was blocked by WM and LY (41±4% and 43±5%, respectively; P<0.05 compared with PC). DOG addition improved postischemic LVDP (67±6%; P<0.001 compared with control), but in contrast to its effect on PC, WM did not completely eliminate the protective effect of DOG (52±4%; P>0.05 compared with DOG; P<0.05 compared with control). PC induced phosphorylation of protein kinase B and translocation of PKCε, and it increased NO production, and these effects were blocked by WM, which suggests a role for PI3-kinase in PC upstream of PKC and NO.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalCirculation Research
Volume87
Issue number4
StatePublished - Aug 18 2000

Fingerprint

Phosphatidylinositol 3-Kinase
Ischemic Preconditioning
Glycerol
Protein Kinase C
Ischemia
Proto-Oncogene Proteins c-akt
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Ventricular Pressure
Protein Transport
Perfusion
Phosphorylation
wortmannin

Keywords

  • Ischemic preconditioning
  • Nitric oxide
  • Phosphatidylinositol 3-kinase
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. / Tong, Haiyan; Chen, Weina; Steenbergen, Charles; Murphy, Elizabeth.

In: Circulation Research, Vol. 87, No. 4, 18.08.2000, p. 309-315.

Research output: Contribution to journalArticle

Tong, Haiyan ; Chen, Weina ; Steenbergen, Charles ; Murphy, Elizabeth. / Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. In: Circulation Research. 2000 ; Vol. 87, No. 4. pp. 309-315.
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