p38 MAPK as a negative regulator of VEGF/VEGFR2 signaling pathway in serum deprived human SK-N-SH neuroblastoma cells

Neuroscience Letters
Evan Gomes, Patricia Rockwell

Abstract

Evidence suggests that vascular endothelial growth factor (VEGF) mediates neuroprotection to prevent an apoptotic cell death. The p38 mitogen-activated protein kinase (MAPK) pathway is implicated as an important mediator of neuronal apoptosis but its role in VEGF-mediated neuroprotection is unclear. Herein, we show that treatments with the p38 MAPK inhibitor, SB202190, enhanced VEGF-mediated survival in serum deprived SK-N-SH neuroblastoma cells by decreasing caspase-3/7 activation while increasing the phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and Akt signaled through the VEGF receptor, VEGFR2. A blockade of VEGFR2 signaling with a selective inhibitor, SU1498 or gene silencing with VEGFR2 siRNA in SB202190 treated cells abrogated this prosurvival response and induced high activation levels of caspase-3/7. These findings suggested that the protection elicited by p38 MAPK inhibition in serum starved cells was dependent on a functional VEGF/VEGFR2 pathway. However, p38 MAPK inhibition attenuated caspase-3 cleavage in SU1498/SB202190 treated cells, indicating that p38 MAPK and caspase-3 only contributed in part to the total levels of caspase-3/7 induced by VEGFR2 inhibition. Pretreatments with the pan ca...Continue Reading

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Citations

Jul 7, 2009·European Archives of Psychiatry and Clinical Neuroscience·Gerburg KeilhoffAxel Becker
Jul 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ina M WittkoKarl H Plate
Aug 31, 2011·Journal of Oncology·Subhasree Roy ChoudhurySwapan K Ray
Oct 16, 2015·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Y LiuX Jiang
Jan 26, 2013·Brain Research·Sudarshan PhaniLorraine Iacovitti
Jan 1, 2013·Critical Reviews in Oncology/hematology·Domenico Ribatti
Apr 4, 2009·Physiological Reviews·Carmen Ruiz de AlmodovarPeter Carmeliet
Dec 27, 2011·Molecular and Cellular Biochemistry·Osamu KoshioKazuo Suzuki
Mar 7, 2021·International Journal of Molecular Sciences·Wineke BakkerMarie José T H Goumans
May 25, 2021·Frontiers in Pharmacology·Grazia MaugeriSalvatore Giunta

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