cAMP/PKA Signaling Pathway Induces Apoptosis by Inhibited NF-κB in Aluminum Chloride-Treated Lymphocytes In Vitro

Abstract

To explore the apoptosis mechanism in lymphocytes of rats induced by aluminum chloride (AlCl3) by activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, the splenic lymphocytes of rats were cultured and exposed to different concentrations of AlCl3 for 24 h. The final concentrations of AlCl3 (AlCl3 · 6H2O) in supernatant were 0 (control group, CG), 0.3 mmol/L (low-dose group, LG), 0.6 mmol/L (mid-dose group, MG), and 1.2 mmol/L (high-dose group, HG), respectively. Lymphocytes Apoptosis rate, intracellular cAMP content, PKA, survivin, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2-associated X protein (Bax) mRNA expressions, and the mRNA and protein expressions of nuclear factor-κ-gene binding (NF-κB, p65) were detected, respectively. The results showed that apoptosis index of lymphocytes, cAMP content in intracellular and PKA mRNA expression were significantly upregulated, whereas NF-κB and survivin mRNA expressions, nuclear NF-κB (p65) protein expression, and the ratio of Bcl-2 and Bax mRNA expression were downregulated in the AlCl3-treated groups compared with those in CG. The results indicated that the activated cAMP/PKA signaling pathway induces apoptosis by inhibited NF-κB in AlCl3-treated lymphocytes in vitro.

Inhibition of microRNA-200a Upregulates the Expression of Striatal Dopamine Receptor D2 to Repress Apoptosis of Striatum via the cAMP/PKA Signaling Pathway in Rats with Parkinson’s Disease

“…Importantly, a prior study revealed that the inhibition of miR-200a mitigated apoptosis resulting from oxygenglucose deprivation/reperfusion by repressing p53 and cytochrome c and reducing the Bax/Bcl-2 ratio [10]. CAMP can induce the activation of PKA, while PKA can repress nuclear factor-κ-gene binding, which can mediate apoptotic target genes, including Bcl-2, Bax and survivin, thereby promoting lymphocyte apoptosis [44]. Consistent with our results, mice treated with bucladesine, which is a cAMP agonist, have been shown to exhibit significantly [45].…”

Metabotropic glutamate receptor 3 is involved in B-cell-related tumor apoptosis

“…Grm3, a group II receptor, is linked to the inhibition of the cyclic AMP cascade. Some literature demonstrates that cAMP/protein kinase A (PKA) induces apoptosis such as in immature T cells by inducing pro-apoptotic protein BIM (33), in aluminum chloride-treated lymphocytes by inhibiting NF-κB (34). Other studies suggest that elevation of cAMP levels inhibits apoptosis such as in doxorubicin-treated Nalm-6 cells through induction of BAD phosphorylation and inhibition of p53 accumulation (35), in arsenic trioxide-treated acute promyelocytic leukemia cells by blocking caspase-3 activation (36).…”

Pivotal role of cAMP‐PKA‐CREB signaling pathway in manganese‐induced neurotoxicity in PC12 cells

“…These results suggest that the decrease of cAMP signaling mediated neuron apoptosis. However, some evidence showed that decreasing cAMP signaling can inhibit apoptosis of lymphoid cells, cardiac myocytes, and so on, 14,43 suggesting that the cAMP signaling could be both proapoptotic and antiapoptotic, and whether it promotes apoptosis or stimulates cell survival is cell type-dependent. 43 BDNF, a downstream gene of cAMP signaling, mediated by CREB, 18 is a well-known regulator in modulating synaptic transmission and plasticity, memory development, and storage.…”

“…Neuronal apoptosis is considered to be one of the mechanisms of Mn‐induced neurotoxicity, which involves Bcl‐2 family‐mediated mitochondrial dysfunction, cytochrome c release, and caspases' activation . Recent evidence suggests that cAMP‐PKA‐CREB signaling regulates apoptosis and is associated with cognitive function . As a second messenger of intracellular signal, cAMP can activate PKA, which can lead to phosphorylation of CREB (pCREB) on Ser133 .…”

“…12,13 Recent evidence suggests that cAMP-PKA-CREB signaling regulates apoptosis and is associated with cognitive function. [14][15][16][17] As a second messenger of intracellular signal, cAMP can activate PKA, which can lead to phosphorylation of CREB (pCREB) on Ser133. 18,19 These processes have been demonstrated as important for the induction and persistence of long-term memory and long-term potentiation.…”