Neuroprotective effects of Argon are mediated via an <scp>ERK</scp>‐1/2 dependent regulation of heme‐oxygenase‐1 in retinal ganglion cells

Ulbrich, Felix; Kaufmann, Kai; Coburn, Mark; Lagrèze, Wolf A.; Roesslein, Martin; Biermann, Julia; Buerkle, Hartmut; Loop, Torsten; Goebel, Ulrich

doi:10.1111/jnc.13115

Cited by 44 publications

(68 citation statements)

References 45 publications

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“…ERK1/2 is activated by various growth factors, and also apparently positively influenced by argon [22,23,24]. In contrast, we found no significant differences for ERK1/2 on the protein level.…”

Section: Discussioncontrasting

confidence: 54%

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Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

et al. 2017

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Background: The liver can heal up to restitutio ad integrum following damage resulting from various causes. Different studies have demonstrated the protective effect of argon on various cells and organs. To the best of our knowledge, the organ-protective effects of the noble gas argon on the liver have not yet been investigated, although argon appears to influence signal paths that are well-known mediators of liver regeneration. We hypothesized that argon inhalation prior to partial hepatectomy (70%) has a positive effect on the initiation of liver regeneration in rats. Methods: Partial hepatectomy (70%) with or without inhaled argon (50 vol%) was performed for 1 h. Liver tissue was harvested after 3, 36, and 96 h to analyze the mRNA and protein expression of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α, and extracellular signal-regulated kinase 1/2. Histological tissue samples were prepared for immunohistochemistry (bromodeoxyuridine [BrdU], Ki-67, and TUNEL) and blood was analyzed regarding the effects of argon on liver function. Statistical analyses were performed using 1-way ANOVA followed by the post hoc Tukey-Kramer test. Results: After 3 h, the primary outcome parameter of hepatocyte proliferation was significantly reduced with argon 50 vol% inhalation in comparison to nitrogen inhalation (BrdU: 15.7 ± 9.7 vs. 7.7 ± 3.1 positive cells/1,000 hepatocytes, p = 0.013; Ki-67: 17.6 ± 13.3 vs. 4.7 ± 5.4 positive cells/1,000 hepatocytes, p = 0.006). This was most likely mediated by significant downregulation of HGF (after 3 h: 5.2 ± 3.2 vs. 2.3 ± 1.0 fold, p = 0.032; after 96 h: 2.1 ± 0.5 vs. 1.3 ± 0.3 fold, p = 0.029) and IL-6 (after 3 h: 43.7 ± 39.6 vs. 8.5 ± 9.2 fold, p = 0.032). Nevertheless, we could detect no significant effect on the weight of the residual liver, liver-body weight ratio, or liver blood test results after argon inhalation. Conclusion: Impairment of liver regeneration was apparent after argon 50 vol% inhalation that was most probably mediated by downregulation of HGF and IL-6 in the initial phase. However, the present study was not adequately powered to prove that argon has detrimental effects on the liver. Further studies are needed to evaluate the effects of argon on livers with preexisting conditions as well as on ischemia-reperfusion models.

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Section: Discussioncontrasting

confidence: 54%

“…ERK1/2 is crucially involved in LR, and was previously shown to be activated by argon conditioning [22,23,24]. However, Western blot analysis revealed no significant changes following partial hepatectomy with argon after 3, 36, or 96 h (Fig.…”

Section: Resultsmentioning

confidence: 80%

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

et al. 2017

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“…In addition, ERK inhibition using FR180204 directly suspended argon’s effects regarding ERK phosphorylation with subsequent increase in apoptosis in a neuroblastoma cell line, analyzed by Ulbrich et al [38]. In an in vivo model of retinal IRI, Ulbrich et al [45] were able to prove these effects in rats; an inhibition of ERK1/2 administering PD98059 intravenously significantly reduced argon’s neuroprotective effects. The authors were able to show that these ERK1/2-mediated effects are responsible for an increase in caspase-3 cleavage and subsequent in apoptosis.…”

Section: Intracellular Pathways Displaying Argon-mediated Neuropromentioning

confidence: 99%

“…Ulbrich et al [45] examined argon’s influence regarding the expression of heat shock proteins in vivo. After retinal IRI in Sprague-Dawley rats, the 70 and 90 kDa heat shock proteins as well as the heme-oxygenase-1 (HO-1, HSP-32) were markedly increased.…”

Section: Intracellular Pathways Displaying Argon-mediated Neuropromentioning

confidence: 99%

The Molecular Pathway of Argon-Mediated Neuroprotection

Ulbrich

Goebel

2016

IJMS

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The noble gas argon has attracted increasing attention in recent years, especially because of its neuroprotective properties. In a variety of models, ranging from oxygen-glucose deprivation in cell culture to complex models of mid-cerebral artery occlusion, subarachnoid hemorrhage or retinal ischemia-reperfusion injury in animals, argon administration after individual injury demonstrated favorable effects, particularly increased cell survival and even improved neuronal function. As an inert molecule, argon did not show signs of adverse effects in the in vitro and in vivo model used, while being comparably cheap and easy to apply. However, the molecular mechanism by which argon is able to exert its protective and beneficial characteristics remains unclear. Although there are many pieces missing to complete the signaling pathway throughout the cell, it is the aim of this review to summarize the known parts of the molecular pathways and to combine them to provide a clear insight into the cellular pathway, starting with the receptors that may be involved in mediating argons effects and ending with the translational response.

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“…Previous reports have shown that the ERK1/2 signaling pathway is activated during oxidative stress and that ERK1/2 phosphorylation plays a key role in mediating cell survival/cell death, depending on stimulus duration and cell type 41, 42. This dual role of the ERK1/2 signaling pathway has also been observed in OLs.…”

Section: Discussionmentioning

confidence: 74%

Catalpol Protects Pre-Myelinating Oligodendrocytes against Ischemia-induced Oxidative Injury through ERK1/2 Signaling Pathway

Cai¹,

Ma²,

Li³

et al. 2016

Int. J. Biol. Sci.

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The vulnerability of pre-myelinating oligodendrocytes (PreOLs) to ischemic injury plays an important role in the pathogenesis and progression of perinatal white matter injury. Although oxidative stress is thought to be a major pathogenic mechanism predisposing the PreOLs to injury, no effective therapies have been identified to date. The present study aimed to investigate the direct protective effects of catalpol, a potent antioxidant and free radical scavenger, on ischemia-induced oxidative damage in PreOLs and to explore whether the ERK1/2 signaling pathway contributed to the protection provided by catalpol. Primary cultures of PreOLs exposed to oxygen-glucose deprivation (OGD) followed by reperfusion were used as an in vitro model of ischemia. Pretreatment with 0.5 mM catalpol for 1 h prior to OGD treatment significantly reversed ischemia-induced apoptosis in PreOLs and myelination deficits by inhibiting intracellular Ca2+ increase, reducing mitochondrial damage, and ameliorating overproduction of reactive oxygen species (ROS). The expression levels of phosphorylated ERK1/2 (p-ERK1/2) and activated poly-ADP-ribose polymerase-1 (PARP-1) were also markedly decreased by catalpol treatment. Blocking the ERK1/2 signaling pathway with the MEK inhibitor U0126 and catalpol significantly protected PreOLs from ROS-mediated apoptosis under OGD. Taken together, these results suggest that catalpol protects PreOLs against ischemia-induced oxidative injury through ERK1/2 signaling pathway. Catalpol may be a candidate for treating ischemic white matter damage.

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Neuroprotective effects of Argon are mediated via an ERK‐1/2 dependent regulation of heme‐oxygenase‐1 in retinal ganglion cells

Cited by 44 publications

References 45 publications

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

The Molecular Pathway of Argon-Mediated Neuroprotection

Catalpol Protects Pre-Myelinating Oligodendrocytes against Ischemia-induced Oxidative Injury through ERK1/2 Signaling Pathway

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