cCMP causes caspase-dependent apoptosis in mouse lymphoma cell lines
作者： Sabine Wolter , Christina Kloth , Marina Golombek , Fanni Dittmar , Lisa Försterling
DOI: 10.1016/J.BCP.2015.08.096
关键词:
摘要: cCMP is a cyclic pyrimidine nucleotide which binds to and activates cAMP-dependent protein kinase (PKA) cGMP-dependent (PKG). In S49 lymphoma cells, cAMP induces apoptosis via PKA. our present study, we examined the effect of on in mouse cells PKA-deficient S49kin(-)cells. These two cell lines also lack PKG, hyperpolarization-activated nucleotide-gated channels 2 4 (HCN2 HCN4) as assessed by real-time PCR. The cell-permeable analog cCMP-AM induced PKA- PKG-independent cells. contrast, exchange activated (Epac) activation did not induce apoptosis. caspase-dependent intrinsic pathway, led cytochrome c release from mitochondria ER stress pathway. On contrary, extrinsic apoptotic pathway was involved. Autophagy detectable after treatment with both lines. cAMP-AM, cGMP-AM, cUMP-AM well nucleotides lacking acetoxymethylester (AM)-group had no effect. altered gene expression apoptotic-relevant Gadd45α immediate early response genes cFos Nr4A1 wild-type (wt) conclusion, independently hitherto known target proteins.
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