bp(GO:"MAPK cascade")
Intraneuronal Abeta can also impair amygdala-dependent emotional responses by affecting the ERK/MAPK signaling pathway [153] PubMed:21214928
Furthermore, TNF-alpha strongly promotes ligand-mediated upregulation of alpha4beta2 nAChRs through a mechanism that requires p38 mitogen-activated protein kinase (MAPK) signaling (163). PubMed:19126755
In cell lines, this interaction of trans-activating components is also under the regulation of the Ras-dependent MAPK and pathways related to phosphoinositide-3-kinase (PI3K) and MEK activation whose response to trophic factors such as nerve growth factor (NGF) contributes to regulating transcript initiation. PubMed:19126755
Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145
Application of nicotine to rat microglia results in the up-regulated expression of cyclooxygenase-2 and prostaglandin E2 (De Simone et al., 2005). Signaling pathways downstream to the MAPK pathway are similarly well placed to effect changes in gene expression. For example, alpha7-dependent activation of the MAPK pathway is known to activate c-Myc (Liu et al., 2007), a protooncogene whose transcription product sensitizes cells to pro-apoptotic stimuli. PubMed:19293145
Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145
Nicotine may regulate the neuroprotective secretion of TNFalpha by microglia through enhancement of lowlevel TNF secretion and suppression of lipopolysaccharide- induced TNFalpha secretion (Suzuki et al., 2006; Park et al., 2007) via alpha7-dependent activation of JNK and MAPK pathways. PubMed:19293145
Paradoxically, Abeta also activates the MAPK pathway through an alpha7-dependent pathway (Dineley et al., 2001; Bell et al., 2004). In human oral keratinocytes, the Ras/Raf/mitogen-activated protein kinase kinase 1/ERK pathway cooperates with the nicotine activation of the JAK/STAT-3 pathway (Arredondo et al., 2006); the Ras pathway induces STAT-3 upregulation whereas the JAK/STAT-3 pathway phosphorylates STAT-3. PubMed:19293145
When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577
Then the stimulation of RAGE is able to activate the mitogen-activated protein kinase signaling cascades which converge in IκB kinase complex to phosphorylate IκB, thereby release and activate NF-κB, thus trigger NF-κB dependent gene transcription including IL-1β and TNF-α, which in turn induce the translocation of NF-κB to the nucleus [50]. PubMed:27288790
Reports have indicated that MAPK signaling pathways are excessively activated in AD. PubMed:27288790
Intraneuronal Abeta can also impair amygdala-dependent emotional responses by affecting the ERK/MAPK signaling pathway [153] PubMed:21214928
Furthermore, TNF-alpha strongly promotes ligand-mediated upregulation of alpha4beta2 nAChRs through a mechanism that requires p38 mitogen-activated protein kinase (MAPK) signaling (163). PubMed:19126755
In cell lines, this interaction of trans-activating components is also under the regulation of the Ras-dependent MAPK and pathways related to phosphoinositide-3-kinase (PI3K) and MEK activation whose response to trophic factors such as nerve growth factor (NGF) contributes to regulating transcript initiation. PubMed:19126755
In lung cancer cells, nicotine also exerts an antiapoptotic effect through activating BCL2-antagonist of cell death (BAD), a process that is inhibited by blockers of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway or the PI3K/AKT pathway (Jin et al., 2004). PubMed:19293145
Application of nicotine to rat microglia results in the up-regulated expression of cyclooxygenase-2 and prostaglandin E2 (De Simone et al., 2005). Signaling pathways downstream to the MAPK pathway are similarly well placed to effect changes in gene expression. For example, alpha7-dependent activation of the MAPK pathway is known to activate c-Myc (Liu et al., 2007), a protooncogene whose transcription product sensitizes cells to pro-apoptotic stimuli. PubMed:19293145
Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145
Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145
Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145
Nicotine also activates ERK in non-neuronal cells such as pancreatic acinar cells (Chowdhury et al., 2007) and vascular smooth muscle cells (Kanda and Watanabe, 2007), although it is not known in those cases which nAChR subtypes are involved. In the cortex and hippocampus of mice, nicotine’s inhibition of MAPK (shown by RNAi reduction of alpha7 expression to be alpha7-dependent) prevents activation of nuclear factor- kappaB and c-Myc, also thereby reducing the activity of inducible nitric-oxide synthetase and NO production and decreasing Abeta production (Liu et al., 2007). PubMed:19293145
When APP/PS1/tau triple transgenic (3×Tg) AD mice are treated with the selective M1 mAChR agonist AF267B, the endogenous level of BACE1 decreases via an unclear mechanism, accompanied by a decreased Abeta level[77]. However, another study found that stimulation of M1 mAChR upregulates BACE1 levels in SK-SH-SY5Y cells via the PKC and MAPK signaling cascades[78]. We recently found that M1 mAChR directly interacts with BACE1 and mediates its proteasomal degradation[79]. These results suggest that M1 mAChR modulates BACE1 in a mixed manner. PubMed:24590577
Reports have indicated that MAPK signaling pathways are excessively activated in AD. PubMed:27288790
Then the stimulation of RAGE is able to activate the mitogen-activated protein kinase signaling cascades which converge in IκB kinase complex to phosphorylate IκB, thereby release and activate NF-κB, thus trigger NF-κB dependent gene transcription including IL-1β and TNF-α, which in turn induce the translocation of NF-κB to the nucleus [50]. PubMed:27288790
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.