Subanesthetic Isoflurane Reduces Zymosan-Induced Inflammation in Murine Kupffer Cells by Inhibiting ROS-Activated p38 MAPK/NF-<i>κ</i>B Signaling

Wang, Hui; Wang, Lei; Li, Nanlin; Li, Juntang; Feng, Yuping; Zhao, Yali; Wang, Ling; Yi, Jun; Bian, Jiefang; Chen, Jianghao; Yuan, Shengtao; Wang, Ting; Lv, Yonggang; Liu, Ningning; Zhu, Xiaoshan; Ling, Rui; Yun, Jae Kwang

doi:10.1155/2014/851692

Cited by 42 publications

(38 citation statements)

References 47 publications

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“…Reactive oxygen species, as a signalling factor, is related to some intracellular pathways, many of which are involved in the regulation of cell senescence . The JNK/p38 pathway plays a crucial role in cell aging, and can be activated by ROS . Therefore, we hypothesized that ROS/JNK/p38 signalling activation is the mechanism by which autophagy inhibits MSC aging induced by D‐gal.…”

Section: Discussionmentioning

confidence: 99%

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Zhang

Chen

et al. 2019

Clin Exp Pharma Physio

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Autophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up-or down-regulation of autophagy by using rapamycin (Rapa) or 3-methyladenine, respectively, before MSC senescence induced by D-galactose (D-gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D-gal and inhibited ROS generation. p-Jun N-terminal kinases (JNK) and p-38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H 2 O 2 on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D-gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagydelaying MSC senescence. K E Y W O R D S autophagy, mesenchymal stem cells, ROS/JNK/p38 signalling, senescence S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Zhang D, Chen Y, Xu X, et al. Autophagy inhibits the mesenchymal stem cell aging induced by D-galactose through ROS/JNK/p38 signalling. Clin Exp Pharmacol Physiol. 2020;47:466-477. https ://doi.

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Section: Discussionmentioning

confidence: 99%

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Zhang

Chen

et al. 2019

Clin Exp Pharma Physio

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“…However, ROS, as a kind of signaling factor, are related with some intracellular pathways [31, 61, 62]; many of these signaling pathways are involved in regulation of cell senescence [63]. The Akt/mTOR pathway plays a crucial role in stem cell aging [64, 65], and this signaling could be inhibited by ROS in cancer cells [66, 67].…”

Section: Discussionmentioning

confidence: 99%

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Zhang

Yan

et al. 2015

Oxidative Medicine and Cellular Longevity

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Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10) plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal) can remarkably induce mesenchymal stem cell (MSC) aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.

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“…Prospects for the clinical usage of isoflurane (1.2-2.5%) have been hampered due to its adverse systemic effects [11]; however, our previous studies have shown that subanesthetic isoflurane (0.7%) protects against zymosan-induced lung injury by upregulating antioxidant enzymes and inhibiting inflammatory responses via the reduction of iNOS induction and NO production in neutrophils [7]. Moreover, subanesthetic isoflurane reduces zymosan- induced inflammation in Kupffer cells by inhibiting the NF-κB pathway [13]. In addition, isoflurane preserves ATP-sensitive K + channel activity in the human omental artery during oxidative stress induced by high glucose, which is mediated by NADPH oxidase inhibition [14].…”

Section: Introductionmentioning

confidence: 99%

Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling

Wang

Wang³

et al. 2016

Oncotarget

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Neutrophil release of NO/ONOO− induces endothelial cell barrier dysfunction in inflammatory acute lung injury (ALI). Previous studies using zymosan-triggered inflammation and ALI model revealed that zymosan promotes inducible NO synthase (iNOS) expression in neutrophils, and that isoflurane inhibits zymosan-induced oxidative stress and iNOS biosynthesis. However, the underlying mechanisms remain largely unknown. We found here that in zymosan-primed neutrophils, iNOS is transcriptionally activated by NF-κB, whose nuclear translocation is triggered by excessive reactive oxygen species (ROS) and consequently activated p38 MAPK. ROS production is attributed to zymosan-initiated Toll-like receptor 2 (TLR2) signaling, in which the adaptor MyD88 recruits and activates c-Src, and c-Src activates NADPH oxidase to generate ROS. Subanesthetic isoflurane counteracts the aforementioned zymosan-induced signaling by targeting N-methyl-D-aspartic acid (NMDA) glutamate receptor and thereby suppressing calcium influx and c-Src activation. Whereas iNOS accelerates NO/ONOO− production in neutrophils which eventually promote protein leak from pulmonary microvascular endothelial cells (PMVEC), isoflurane reduced NO/ONOO− release from zymosan-treated neutrophils, and thus relieves trans- PMVEC protein leak. This study provides novel insights into the roles of neutrophils and the underlying mechanisms in zymosan-induced ALI, and has implications for the therapeutic potential of subanesthetic isoflurane in attenuating inflammatory responses causing lung endothelial cell damage.

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Subanesthetic Isoflurane Reduces Zymosan-Induced Inflammation in Murine Kupffer Cells by Inhibiting ROS-Activated p38 MAPK/NF-κB Signaling

Cited by 42 publications

References 47 publications

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

Subanesthetic isoflurane relieves zymosan-induced neutrophil inflammatory response by targeting NMDA glutamate receptor and Toll-like receptor 2 signaling

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