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Herkinorin negatively regulates NLRP3 inflammasome to alleviate neuronal ischemic injury through activating Mu opioid receptor and inhibiting the NF-kappa B pathway

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收录情况： ◇ SCIE ◇ 预警期刊

作者：
Cui, Xu[1] * ; Xu, Xin[1] ; Ju, Zhihai[1] ; Wang, Guyan[1,*1] ; Xi, Chunhua[1] ; Li, Junfa[2,3,*2] ;
机构： [1]Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China [2]Department of Neurobiology and Center of Stroke, School of Basic Medical Science, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
出处：
DOI： 10.1002/jcb.29929
ISSN：

关键词： Herkinorin Iκ Bα NF‐ κ B pathway NOD‐ like receptor protein 3 (NLRP3) oxygen‐ glucose deprivation (OGD) β ‐ arrestin2

摘要：
Herkinorin is a novel opioid receptor agonist. Activation of opioid receptors, a member of G protein coupled receptors (GPCRs), may play an important role in Herkinorin neuroprotection. GPCRs may modulate NOD-like receptor protein 3 (NLRP3)-mediated inflammatory responses in the mechanisms of inflammation-associated disease and pathological processes. In this study, we investigated the effects of Herkinorin on NLRP3 and the underlying receptor and molecular mechanisms in oxygen-glucose deprivation/reperfusion (OGD/R)-treated rat cortex neurons. First, Western blot analysis showed that Herkinorin can inhibit the activation of NLRP3 and Caspase-1, decrease the expression of interleukin (IL)-1 beta, and decrease the secretion of IL-6 and tumour necrosis factor alpha detected by enzyme-linked immunosorbent assay in OGD/R-treated neurons. Then we found that Herkinorin downregulated NLRP3 levels by inhibiting the activation of nuclear factor kappa B (NF-kappa B) pathway, reducing the phosphorylation level of p65 and I kappa B alpha in OGD/R-treated neurons (p < .05 or .01, n = 3 per group). Instead, both the mu opioid receptor (MOR) inhibitor, beta-funaltrexamine, and MOR knockdown reversed the effects of Herkinorin on NLRP3 (p < .05 or .01, n = 3 per group). Further, we found that the level of beta-arrestin2 decreased in the cell membrane and increased in the cytoplasm after Herkinorin pretreatment in OGD/R-treated neurons. In co-immunoprecipitation experiments, Herkinorin increased the binding of I kappa B alpha with beta-arrestin2, decreased the ubiquitination level of I kappa B alpha, and beta-arrestin2 knockdown reversed the effects of Herkinorin on I kappa B alpha in OGD/R-treated neurons (p < .05 or .01, n = 3 per group). Our data demonstrated that Herkinorin negatively regulated NLRP3 inflammasome to alleviate neuronal ischemic injury through inhibiting NF-kappa B pathway mediated primarily by MOR activation. Inhibition of the NF-kappa B pathway by Herkinorin may be achieved by decreasing the ubiquitination level of I kappa B alpha, in which beta-arrestin2 may play an important role.

基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81301065]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类 | 3 区 生物
小类 | 3 区 生化与分子生物学 3 区 细胞生物学
最新[2023]版：
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 4 区 细胞生物学
JCR分区：
出版当年[2019]版：
Q2 CELL BIOLOGY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

第一作者：
第一作者机构： [1]Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构： [1]Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, China [2]Department of Neurobiology and Center of Stroke, School of Basic Medical Science, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China [*1]Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, #1 Dongjiaominxiang, Dongcheng District, Beijing 100730, China. [*2]Department of Neurobiology, Capital Medical University, #10 You An Men Wai Xi Tou Tiao, Beijing 100069, China.
推荐引用方式(GB/T 7714)：
Cui Xu,Xu Xin,Ju Zhihai,et al.Herkinorin negatively regulates NLRP3 inflammasome to alleviate neuronal ischemic injury through activating Mu opioid receptor and inhibiting the NF-kappa B pathway[J].JOURNAL OF CELLULAR BIOCHEMISTRY.2021,122(9):1085-1097.doi:10.1002/jcb.29929.
APA：
Cui, Xu,Xu, Xin,Ju, Zhihai,Wang, Guyan,Xi, Chunhua&Li, Junfa.(2021).Herkinorin negatively regulates NLRP3 inflammasome to alleviate neuronal ischemic injury through activating Mu opioid receptor and inhibiting the NF-kappa B pathway.JOURNAL OF CELLULAR BIOCHEMISTRY,122,(9)
MLA：
Cui, Xu,et al."Herkinorin negatively regulates NLRP3 inflammasome to alleviate neuronal ischemic injury through activating Mu opioid receptor and inhibiting the NF-kappa B pathway".JOURNAL OF CELLULAR BIOCHEMISTRY 122..9(2021):1085-1097

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