α7 Nicotinic acetylcholine receptor-specific antibody stimulates interleukin-6 production in human astrocytes through p38-dependent pathway

Kalashnyk, Olena; Lykhmus, Olena; Oliinyk, O. S.; Комісаренко, С. В.; Skok, Maryna

doi:10.1016/j.intimp.2014.09.022

Cited by 21 publications

(16 citation statements)

References 33 publications

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“…Our previous studies reported that ACh prevents Ang II-induced apoptosis in H9c2 cells through inhibition of ROS-mediated p38 MAPK activation [7]. Skok et al thought the α7 nicotinic ACh receptor plays an important role in inhibiting p38-MAPK pathway activation [40]. The data presented here indicated that ACh depressed p38-MAPKdependent intracellular signalling resulting in calpain inactivated via M 2 AChR.…”

Section: Discussionsupporting

confidence: 50%

Acetylcholine Attenuated TNF-α-Induced Apoptosis in H9c2 Cells: Role of Calpain and the p38-MAPK Pathway

Zhao

Yang

et al. 2015

Cell Physiol Biochem

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This is an Open Access article licensed under the terms of the Creative Commons AttributionNonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Key Words Acetylcholine • Muscarinic receptor • Calpain • Calpastatin • p38-MAPK • ApoptosisAbstract Background: Previous studies have shown that inflammation is associated with excessive activation of calpains. Acetylcholine (ACh) has been reported to inhibit pro-inflammatory cytokine release and protect against cardiomyocyte injury. However, there is no direct evidence regarding whether ACh can regulate calpains to exert cardioprotection. To this end, we investigated the effect of ACh on tumour necrosis factor alpha (TNF-α)-induced cardiomyocyte injury and further explored the underlying mechanism. Methods: Flow cytometry and transmission electron microscopy were performed to evaluate apoptosis and cellular ultrastructure. Western blotting was performed to assess changes in protein expression. siRNA was employed to silence specific proteins. Results: TNF-α treatment increased the expression of cleaved caspase-3, calpain-1 and p38-mitogen-activated protein kinase (p38-MAPK). The calpain inhibitor PD150606 and the p38-MAPK inhibitor SB203580 inhibited apoptosis induced by TNF-α. Moreover, SB203580 decreased the expression and activity of calpain-1, possibly related to the up-regulation of calpastatin. ACh significantly inhibited TNF-α-induced cell apoptosis, as evidenced by decreases in caspase-3 cleavage, p38-MAPK phosphorylation, and calpain-1 expression and activity as well as increases in calpastatin expression. These beneficial effects of ACh were abolished by atropine or M 2 AChR siRNA. Conclusion: Our results suggest that ACh ameliorated TNF-α-induced calpain activation by decreasing p38-MAPK phosphorylation and enhancing calpastatin expression, indicating that calpain may be an important link between inflammatory factors and myocardial cell apoptosis.M. Zhao and Y. Yang contributed equally to this work.

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Section: Discussionsupporting

confidence: 50%

Acetylcholine Attenuated TNF-α-Induced Apoptosis in H9c2 Cells: Role of Calpain and the p38-MAPK Pathway

Zhao

Yang

et al. 2015

Cell Physiol Biochem

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“…In addition, a 7 nAChRs activation inhibits free radicals-induced GDNF down-regulation in the primary culture astrocytes (Liu et al 2015). Neuroinflammation a 7 nAChRs are involved in the regulation of inflammatory cytokine production in astrocytes (Kalashnyk et al 2014;Niranjan et al 2012). Kalashnyk et al, showed that a 7 -specific agonists decrease interleukin-6 (IL-6) production in astrocyte-derived cell lines.…”

Section: Neuroprotectionmentioning

confidence: 99%

“…In contrast, a 7 -specific antibody could bind to and internalize these receptors in astrocytes and stimulate IL-6 production. The a 7 nAChRs internalization might provoke neuroinflammation within the brain by inducing IL-6 production in astrocytes (Kalashnyk et al 2014). Some studies suggest a close relationship between Ab deposits, inflammation and neurodegeneration at relatively early stages of AD (Eikelenboom et al 2006;Sadigh-Eteghad et al 2015b).…”

Section: Neuroprotectionmentioning

confidence: 99%

Astrocytic and microglial nicotinic acetylcholine receptors: an overlooked issue in Alzheimer’s disease

et al. 2016

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It is increasingly recognized that astrocytes and microglia-associated dysfunction contribute to AD pathology. In addition, glial nicotinic acetylcholine receptors (nAChRs) play a role in AD-related phenomena, such as neuron survival, synaptic plasticity, and memory. From mechanistic point of view, the glial regulation of pro-inflammatory cytokines, as common contributors in AD, is modulated by nAChRs. Astrocytic and microglial nAChRs contribute to Aβ metabolism, including Aβ phagocytosis and degradation as well as Aβ-related oxidative stress and neurotoxicity. These receptors are also involved in neurotransmission and gliotransmission through indirect interaction with N-Methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA) receptors as well as gamma-aminobutyric acid (GABA) and intracellular calcium regulation. In addition, glial nAChRs participate in trophic factors-induced neuroprotection. This review gathers the most recent advances along with the previous data on astrocytic and microglial nAChRs role in AD pathogenesis.

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“…The expression of α7nAChRs in normal mature muscle is minimal. In contrast to muscle expression of α7nAChRs only in pathologic states, the α7nAChRs are constitutively expressed in macrophages and other circulating leucocytes [25, 40, 44, 62]. During inflammation, however, these α7nAChRs are further up-regulated in vitro in macrophages [30] and in vivo in burned patients [51].…”

Section: Introductionmentioning

confidence: 99%

GTS-21 attenuates loss of body mass, muscle mass, and function in rats having systemic inflammation with and without disuse atrophy

Schaller

Nagashima

Schönfelder

et al. 2018

Pflugers Arch - Eur J Physiol

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Muscle changes of critical illness are attributed to systemic inflammatory responses and disuse atrophy. GTS-21 (3-(2,4-dimethoxy-benzylidene)anabaseine), also known as DMBX-A) is a synthetic derivative of the natural product anabaseine that acts as an agonist at α7-acetylcholine receptors (α7nAChRs). Hypothesis tested was that modulation of inflammation by agonist GTS-21 (10 mg/kg b.i.d. intraperitoneally) will attenuate body weight (BW) and muscle changes. Systemic sham inflammation was produced in 125 rats by Cornyebacterium parvum (C.p.) or saline injection on days 0/4/8. Seventy-four rats had one immobilized-limb producing disuse atrophy. GTS-21 effects on BW, tibialis muscle mass (TMM), and function were assessed on day 12. Systemically, methemoglobin levels increased 26-fold with C.p. (p < 0.001) and decreased significantly (p < 0.033) with GTS-21. Control BW increased (+ 30 ± 9 g, mean ± SD) at day 12, but decreased with C.p. and superimposed disuse (p = 0.005). GTS-21 attenuated BW loss in C.p. (p = 0.005). Compared to controls, TMM decreased with C.p. (0.43 ± 0.06 g to 0.26 ± 0.03 g) and with superimposed disuse (0.18 ± 0.04 g); GTS-21 ameliorated TMM loss to 0.32 ± 0.04 (no disuse, p = 0.028) and to 0.22 ± 0.03 (with disuse, p = 0.004). Tetanic tensions decreased with C.p. or disuse and GTS-21 attenuated tension decrease in animals with disuse (p = 0.006) and in animals with C.p. and disuse (p = 0.029). C.p.-induced 11-fold increased muscle α7nAChR expression was decreased by > 60% with GTS-21 treatment. In conclusion, GTS-21 modulates systemic inflammation, evidenced by both decreased methemoglobin levels and decrease of α7nAChR expression, and mitigates inflammation-mediated loss of BW, TMM, fiber size, and function.

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α7 Nicotinic acetylcholine receptor-specific antibody stimulates interleukin-6 production in human astrocytes through p38-dependent pathway

Cited by 21 publications

References 33 publications

Acetylcholine Attenuated TNF-α-Induced Apoptosis in H9c2 Cells: Role of Calpain and the p38-MAPK Pathway

Acetylcholine Attenuated TNF-α-Induced Apoptosis in H9c2 Cells: Role of Calpain and the p38-MAPK Pathway

Astrocytic and microglial nicotinic acetylcholine receptors: an overlooked issue in Alzheimer’s disease

GTS-21 attenuates loss of body mass, muscle mass, and function in rats having systemic inflammation with and without disuse atrophy

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