TY  - JOUR
A1  - Rössig, Lothar
A1  - Haendeler, Judith
A1  - Hermann, Corinna
A1  - Malchow, Philipp
A1  - Urbich, Carmen
A1  - Zeiher, Andreas M.
A1  - Dimmeler, Stefanie
T1  - Nitric oxide down-regulates MKP-3 mRNA levels: involvement in endothelial cell protection from apoptosis
T2  - Journal of biological chemistry
N2  - MAP kinase-dependent phosphorylation processes have been shown to interfere with the degradation of the antiapoptotic protein Bcl-2. The cytosolic MAP kinase phosphatase MAP kinase phosphatase-3 (MKP-3) induces apoptosis of endothelial cells in response to tumor necrosis factor alpha (TNFalpha) via dephosphorylation of the MAP kinase ERK1/2, leading to Bcl-2 proteolysis. Here we report that the endothelial cell survival factor nitric oxide (NO) down-regulated MKP-3 by destabilization of MKP-3 mRNA. This effect of NO was paralleled by a decrease in MKP-3 protein levels. Moreover, ERK1/2 was found to be protected against TNFalpha-induced dephosphorylation by coincubation of endothelial cells with the NO donor. Subsequently, both the decrease in Bcl-2 protein levels and the mitochondrial release of cytochrome c in response to TNFalpha were largely prevented by exogenous NO. In cells overexpressing MKP-3, no differences in phosphatase activity in the presence or absence of NO were found, excluding potential posttranslational modifications of MKP-3 protein by NO. These data demonstrate that upstream of the S-nitrosylation of caspase-3, NO exerts additional antiapoptotic effects in endothelial cells, which rely on the down-regulation of MKP-3 mRNA.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/75841
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-758418
SN  - 0021-9258
VL  - 275
IS  - 33
SP  - 25502
EP  - 25507
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -