Placental expression of AChE, α7nAChR and NF-κB in patients with preeclampsia
Abstract
Objectives: This study aimed to investigate placental expression of AChE, α7nAChR and NF-κB in patients with preeclampsia and discuss about its clinical significance.
Material and methods: mRNA expression levels of acetylcholine (AChE), alpha-7 nicotinic acetylcholine receptor (α7nAChR) and nuclear factor-kB (NF-κB) in placenta were detected by qRT-PCR, and protein levels were determined by immunohistological analysis and Western Blot in 35 women with preeclampsia (including 20 cases of mild preeclampsia and 15 cases of severe preeclampsia) and 30 cases in control group, respectively.
Results: The expression of AChE mRNA and protein in placenta increased significantly in patients with preeclampsia compared with the control group (p < 0.01). It was lower in patients with severe preeclampsia than in patients with mild preeclampsia (p < 0.05). The expression of α7nAChR mRNA and protein in placenta decreased significantly in patients with preeclampsia compared with the control group (p < 0.01). However, the expression of α7nAChR mRNA and protein in patients with severe preeclampsia was higher than that in patients with mild preeclampsia, without significant difference(p > 0.05). The expression of NF-κB protein in placenta decreased significantly in patients with preeclampsia compared with the control group(p < 0.01). It was higher in patients with severe preeclampsia than in patients with mild preeclampsia (p < 0.05), but there was no significant difference between preeclampsia group and control group in the expression of NF-κB mRNA in placenta (p > 0.05). The results of Western blotting assay were consistent with those of immunohistochemistry.
Conclusions: Abnormal expression of AChE, α7nAChR and NF-κB in placenta may be associated with preeclampsia. Cholinergic anti-inflammatory pathway may play an important role in the pathogenesis of preeclampsia.
Keywords: preeclampsiacholinergic anti-inflammatory pathwayAChEα7nAChRNF-κB
References
- Chen GW, Tang YZ, Chen HH, et al. Effect of gestational age and timing of pregnancy termination in early onset severe preeclampsia on perinatal outcome [J]. The Journal of Practical Medicine. 2009; 25(3): 389–391.
- Altavilla D, Guarini S, Bitto A, et al. Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock. Shock. 2006; 25(5): 500–506.
- Pavlov VA, Wang H, Czura CJ, et al. The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med. 2003; 9(5-8): 125–134.
- Pavlov VA, Tracey KJ. Neural regulators of innate immune responses and inflammation. Cell Mol Life Sci. 2004; 61(18): 2322–2331.
- Shi L, Ru MY, Cai WJ. Expression and significance of cholinesterase and cell factor in pre-eclampsia [J]. Hainan Medical Journal. 2013; 24(18): 2663–2664.
- Xie X, Gou WL. Obstetrics and Gynecology [M]. Eighth edition. Beijing: The People's Medical Publishing House. ; 2013: 65–66.
- Roberts CL, Ford JB, Algert CS, et al. Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study. BMJ Open. 2011; 1(1): e000101.
- Qian ZQ, Zeng YY, Zhong B, et al. Detection of systematic oxidative stress in preeclampsia [J]. Basic & Clinical Medicine. 2010; 30(4): 343–347.
- Hamad RR, Eriksson MJ, Berg E, et al. Impaired endothelial function and elevated levels of pentraxin 3 in early-onset preeclampsia. Acta Obstet Gynecol Scand. 2012; 91(1): 50–56.
- Borovikova LV, Ivanova S, Nardi D, et al. Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation. Auton Neurosci. 2000; 85(1-3): 141–147.
- Liu XJ, Mei ZG, Wang MZ. Cholinergic anti-inflammatory pathway: A potential regulatory mechanism of inflammatory response in cerebral ischemic stroke [J]. Chinese Journal of Gerontology. 2013; 33(5): 1211–1213.
- Leib C, Göser S, Lüthje D, et al. Role of the cholinergic antiinflammatory pathway in murine autoimmune myocarditis. Circ Res. 2011; 109(2): 130–140.
- Satyanarayana M. A correlative review of acetylcholine synthesis in relation to histopathology of the human syncytiotrophoblast. Acta Obstet Gynecol Scand. 1986; 65(6): 567–572.
- Murthy NV, Melville GN, Wynter HH, et al. In vitro human placental perfusion studies cholinergic activity in normal subjects and in toxaemia of pregnancy. West Indian Med J. 1985; 34(4): 257–260.
- Samuel GS, Ng YS. A case report on the use of an acetylcholinesterase inhibitor (donepezil) in traumatic brain injury. Med J Malaysia. 2013; 68(4): 376–378.
- Wu J, Jin T, Wang H, et al. Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture. Chin Med J (Engl). 2016; 129(12): 1477–1482.
- Li J, Mathieu SL, Harris R, et al. Role of α7 nicotinic acetylcholine receptors in regulating tumor necrosis factor-α (TNF-α) as revealed by subtype selective agonists. J Neuroimmunol. 2011; 239(1-2): 37–43.
- Hedrick T, Waters J. Acetylcholine excites neocortical pyramidal neurons via nicotinic receptors. J Neurophysiol. 2015; 113(7): 2195–2209.
- Heeschen C, Weis M, Aicher A, et al. A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors. J Clin Invest. 2002; 110(4): 527–536.
- Hua S, Ek CJ, Mallard C, et al. Perinatal hypoxia-ischemia reduces α 7 nicotinic receptor expression and selective α 7 nicotinic receptor stimulation suppresses inflammation and promotes microglial Mox phenotype. Biomed Res Int. 2014; 2014: 718769.
- Souvannakitti D, Kuri B, Yuan G, et al. Neonatal intermittent hypoxia impairs neuronal nicotinic receptor expression and function in adrenal chromaffin cells. Am J Physiol Cell Physiol. 2010; 299(2): C381–C388.
- Machaalani R, Ghazavi E, David RV, et al. Nicotinic acetylcholine receptors (nAChR) are increased in the pre-eclamptic placenta. Hypertens Pregnancy. 2015; 34(2): 227–240.
- Machaalani R, Ghazavi E, Hinton T, et al. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta. Toxicol Appl Pharmacol. 2014; 276(3): 204–212.
- Sharentuya N, Tomimatsu T, Mimura K, et al. Nicotine suppresses interleukin-6 production from vascular endothelial cells: a possible therapeutic role of nicotine for preeclampsia. Reprod Sci. 2010; 17(6): 556–563.
- Saeed RW, Varma S, Peng-Nemeroff T, et al. Cholinergic stimulation blocks endothelial cell activation and leukocyte recruitment during inflammation. J Exp Med. 2005; 201(7): 1113–1123.
- Takacs P, Kauma SW, Sholley MM, et al. Increased circulating lipid peroxides in severe preeclampsia activate NF-kappaB and upregulate ICAM-1 in vascular endothelial cells. FASEB J. 2001; 15(2): 279–281.
- Mahendra J, Parthiban PS, Mahendra L, et al. Evidence Linking the Role of Placental Expressions of Peroxisome Proliferator-Activated Receptor-γ and Nuclear Factor-Kappa B in the Pathogenesis of Preeclampsia Associated With Periodontitis. J Periodontol. 2016; 87(8): 962–970.
- Siwetz M, Dieber-Rotheneder M, Cervar-Zivkovic M, et al. Placental fractalkine is up-regulated in severe early-onset preeclampsia. Am J Pathol. 2015; 185(5): 1334–1343.
- Li XJ. Study on the correlation between onset, degree of severity of preeclampsia and NF-κB, TNF-α, PLGF [J]. Maternal & Child Health Care of China. 2014; 12(29): 1849–1851.
- Khan Z, Ford MJ, Cusanovich DA, et al. Primate transcript and protein expression levels evolve under compensatory selection pressures. Science. 2013; 342(6162): 1100–1104.
- Komili S, Silver PA. Coupling and coordination in gene expression processes: a systems biology view. Nat Rev Genet. 2008; 9(1): 38–48.
- Wu L, Candille SI, Choi Y, et al. Variation and genetic control of protein abundance in humans. Nature. 2013; 499(7456): 79–82.
- Schwanhäusser B, Busse D, Li Na, et al. Global quantification of mammalian gene expression control. Nature. 2011; 473(7347): 337–342.
- Yang E, van Nimwegen E, Zavolan M, et al. Decay rates of human mRNAs: correlation with functional characteristics and sequence attributes. Genome Res. 2003; 13(8): 1863–1872.
- Harbom LJ, Chronister WD, McConnell MJ. Single neuron transcriptome analysis can reveal more than cell type classification: Does it matter if every neuron is unique? Bioessays. 2016; 38(2): 157–161.
