Tyrphostin AG 1478 Accelerates Hydrogen Peroxide-Induced Apoptosis in A431 Cells
Year: 2003
Type: article
Abstract: Oxidative stress is a potent inducer of apoptosis and activates protein tyrosine kinases and cytokine receptors, such as the epidermal growth factor receptor (EGFR). Previous studies suggest that cytokine receptors are potential effectors for anti-apoptotic signals, but it has not previously been determined whether cytokine receptors regulate down-stream protein kinases. To investigate the role of EGFR on oxidative stress-induced apoptosis and its downstream protein kinases, we blocked EGFR activation with Tyrphostin AG1478, a highly selective EGFR inhibitor. We determined that Tyrphostin AG1478 accelerated hydrogen peroxide-induced apoptosis in A431 cells, with activation of caspases 3 and 9, and decreased mitochondrial membrane potential. Hydrogen peroxide induced-activation of EGFR, Akt/PKB, MAPK, and Bad (both Ser-112 and Ser-136 residues) were inhibited by Tyrphostin AG1478. These results suggest that early upstream signaling events, such as EGFR activation, exert anti-apoptotic effects by regulating MAPK, Akt/PKB, and phosphorylation of Bad.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1568054886