Hyperglycemia and reactive oxygen species mediate apoptosis in aortic endothelial cells through Janus kinase 2

Amany Mohamed Tawfik, Liming Jin, Amy K L Banes-Berceli, Ruth B Caldwell, Safia Ogbi, Amanda Shirley, Dwayne Barber, John D. Catravas, David M. Stern, David J Fulton, Robert William Caldwell, Mario B Marrero

Research output: Contribution to journalArticle

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Abstract

The generation of reactive oxygen species (ROS) has been implicated in the perturbation of endothelial function and cell death. However, the specific signaling pathways which mediate and modifying this response have not been fully elucidated. Therefore, in this study we tested the hypothesis that activation of JAK2 is involved in the aortic endothelial cell (EC) response to ROS. When ECs were exposed to HG (25 mM) for 6 h or ROS (i.e., H2O2 (100 μM)) for 1 h and returned to normal medium we found a decrease in cell density and morphologic signs of apoptosis. Furthermore, incubation of ECs with HG and H2O2 also resulted in the tyrosine phosphorylation of JAK2. In addition, pretreatment of ECs with AG-490, an inhibitor of JAK2, prevented nuclear fragmentation, whereas inhibitors of Jun kinase (SP 600125), MAP kinase (PD 98059), Src kinase (PP2) or PI-3 kinase (wortmannin) were without effect. Finally, immunoblot analysis of caspase-3 and PARP cleavage confirmed a role for activation of JAK2 in both HG- or ROS-induced apoptosis, based on inhibition by either AG-490 or adenoviral transfection with a dominant-negative JAK2 mutant. In conclusion the activation of JAK2 plays a pivotal role in oxidant stress-induced commitment of ECs to apoptosis, based on studies with HG and H2O2.

Original languageEnglish (US)
Pages (from-to)320-326
Number of pages7
JournalVascular Pharmacology
Volume43
Issue number5
DOIs
StatePublished - Nov 1 2005

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Janus Kinase 2
Hyperglycemia
Reactive Oxygen Species
Endothelial Cells
Apoptosis
Phosphotransferases
src-Family Kinases
Phosphatidylinositol 3-Kinases
Oxidants
Caspase 3
Transfection
Tyrosine
Cell Death
Cell Count
Phosphorylation
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide

Keywords

  • Apoptosis
  • Endothelial cells
  • JAK2

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hyperglycemia and reactive oxygen species mediate apoptosis in aortic endothelial cells through Janus kinase 2. / Tawfik, Amany Mohamed; Jin, Liming; Banes-Berceli, Amy K L; Caldwell, Ruth B; Ogbi, Safia; Shirley, Amanda; Barber, Dwayne; Catravas, John D.; Stern, David M.; Fulton, David J; Caldwell, Robert William; Marrero, Mario B.

In: Vascular Pharmacology, Vol. 43, No. 5, 01.11.2005, p. 320-326.

Research output: Contribution to journalArticle

Tawfik, Amany Mohamed ; Jin, Liming ; Banes-Berceli, Amy K L ; Caldwell, Ruth B ; Ogbi, Safia ; Shirley, Amanda ; Barber, Dwayne ; Catravas, John D. ; Stern, David M. ; Fulton, David J ; Caldwell, Robert William ; Marrero, Mario B. / Hyperglycemia and reactive oxygen species mediate apoptosis in aortic endothelial cells through Janus kinase 2. In: Vascular Pharmacology. 2005 ; Vol. 43, No. 5. pp. 320-326.
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