Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response...

Area of Science:

• Molecular Biology
• Cellular Biology
• Biochemistry

Background:

• Endothelial nitric oxide synthase (eNOS) plays a crucial role in vascular function.
• Cellular responses to radiation, including kinase activation, are complex and not fully understood.
• Ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) are key regulators of cellular stress responses.

Purpose of the Study:

• To investigate the role of ATM kinase and HSP90 in the activation of eNOS following X-irradiation.
• To elucidate the signaling pathways linking radiation exposure to eNOS activation in endothelial cells.

Main Methods:

• Bovine aortic endothelial cells were subjected to X-irradiation.
• Nitric oxide synthase (NOS) activity and eNOS phosphorylation at serine 1179 (eNOS-Ser1179) were measured.
• The effects of ATM inhibitor (Ku-60019) and HSP90 inhibitor (geldanamycin) on NOS activity and eNOS phosphorylation were assessed.

Main Results:

• X-irradiation significantly increased NOS activity and eNOS-Ser1179 phosphorylation in bovine aortic endothelial cells.
• Treatment with ATM inhibitor (Ku-60019) or HSP90 inhibitor (geldanamycin) significantly reduced radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation.
• Geldanamycin also suppressed radiation-induced phosphorylation of ATM at serine 1181 (ATM-Ser1181).

Conclusions:

• ATM kinase and HSP90 are critical regulators of radiation-induced eNOS activation in bovine aortic endothelial cells.
• These findings highlight a novel signaling pathway involving ATM and HSP90 in the cellular response to radiation, impacting vascular function.