cAMP/PKA Signaling Pathway Induces Apoptosis by Inhibited NF-κB in Aluminum Chloride-Treated Lymphocytes In Vitro.
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.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Feibo
F
Xu
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Jing
J
Wang
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Zheng
Z
Cao
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Miao
M
Song
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Yang
Y
Fu
Institute of Special Economic Animal and Plant Science, Chinese Academy of Agricultural Sciences, Changchun, 130112, China.
Yanzhu
Y
Zhu
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. liyanfei@neau.edu.cn.
Yanfei
Y
Li
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002712:Chlorides / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017607:Aluminum Compounds; C494828:Bax protein, rat; D002712:Chlorides; D019253:Proto-Oncogene Proteins c-bcl-2; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D000077410:Aluminum Chloride; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases
AlCl3; Lymphocytic apoptosis; NF-κB; cAMP/PKA signal pathway