2-Arachidonylglycerol Protects Primary Astrocytes Exposed to Oxygen-Glucose Deprivation Through a Blockade of NDRG2 Signaling and STAT3 Phosphorylation

Wang, Feng; Mo, Li; Li, Xin; Kinden, Renée; Zhou, Haoming; Guo, Fan; Wang, Qiang; Xiong, Lize

doi:10.1089/rej.2015.1703

Cited by 10 publications

(7 citation statements)

References 37 publications

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“…2-AG also seems to reduce the astrocytic production of chondroitin sulfate proteoglycan, that accumulates in MS lesions and is thought to be linked to the failure to regenerate, impeding oligodendrocyte precursor cell differentiation, and neuronal growth [ 154 ]. Moreover, 2-AG protects astrocytes exposed to oxygen-glucose deprivation through a blockade of NDRG2 signaling and STAT3 phosphorylation [ 155 ]. 2-AG and PEA have been shown to attenuate amyloid β-induced astrocyte activation and PEA increased 2-AG production in astrocytes [ 156 , 157 , 158 ].…”

Section: Neuroinflammation-induced Synaptopathy and Neurodegenerative Diseasesmentioning

confidence: 99%

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Kasatkina

Rittchen

Sturm

2021

IJMS

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Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB1/2, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB1/2, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy.

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Section: Neuroinflammation-induced Synaptopathy and Neurodegenerative Diseasesmentioning

confidence: 99%

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Kasatkina

Rittchen

Sturm

2021

IJMS

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“…In this study, we discovered that NDRG2 promoted the expression of p-STAT3, and STAT3 knockdown attenuated the antiapoptotic effect of NDRG2 in photoreceptors. Although the NDRG2-mediated promotion of p-STAT3 expression has been reported in astrocytes, the specific molecular mechanism remains unclear [36,37]. Previous studies have demonstrated that NDRG2 exerts regulatory control over the expression of cytokines, including interleukin-6 (IL-6), IL-1b, IL-10, and the leukocyte inhibitory factor [54][55][56][57].…”

Section: Discussionmentioning

confidence: 99%

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Chen,

Xiong,

Deng

et al. 2023

The FEBS Journal

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Photoreceptor apoptosis is the main pathological feature of retinal degenerative diseases; however, the underlying molecular mechanism has not been elucidated. Recent studies have shown that N‐myc downstream regulated gene 2 (NDRG2) exerts a neuroprotective effect on the brain and spinal cord. In addition, our previous studies have confirmed that NDRG2 is expressed in mouse retinal photoreceptors and counteracts N‐methyl‐N‐nitrosourea (MNU)‐induced apoptosis. However, the underlying molecular mechanism remains unclear. In this study, we observed that the expression of NDRG2 was not only significantly inhibited in photoreceptors after MNU treatment but also after hydrogen peroxide treatment, and photoreceptor apoptosis was alleviated or aggravated after overexpression or knockdown of NDRG2 in the 661W photoreceptor cell line, respectively. The apoptosis inhibitor Z‐VAD‐FMK rescued photoreceptor apoptosis induced by MNU after NDRG2 knockdown. Next, we screened and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as the downstream molecule of NDRG2 in 661W cells by using quantitative real‐time polymerase chain reaction. TIMP3 exerts a neuroprotective effect by inhibiting the expression of matrix metalloproteinases (MMPs). Subsequently, we found that signal transducer and activator of transcription 3 (STAT3) mediated the NDRG2‐associated regulation of TIMP3. Finally, we overexpressed NDRG2 in mouse retinal tissues by intravitreally injecting an adeno‐associated virus with mouse NDRG2 in vivo. Results showed that NDRG2 upregulated the expression of phospho‐STAT3 (p‐STAT3) and TIMP3, while suppressing MNU‐induced photoreceptor apoptosis and MMP expression. Our findings revealed how NDRG2 regulates the STAT3/TIMP3/MMP pathway and uncovered the molecular mechanism underlying its neuroprotective effect on mouse retinal photoreceptors.

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“…Reducing JAK2/STAT3 phosphorylation can decrease neuronal death, narrow infarct size and prevent post-ischemic damage of nerve cells. Wang et al reported a significant neuroprotective effect by reducing the phosphorylation of STAT3 following cerebral ischemia through RNA interference (38). Others have found that electroacupuncture stimulation of focal cerebral ischemia at the Baihui acupoint and Dazhui acupoint in rats relieved nerve function deficit by reducing the expression of JAK2, preventing abnormal JAK2 activation and downregulating the phosphorylation of STAT3 (37).…”

Section: Discussionmentioning

confidence: 99%

Kappa opioid receptor agonists improve postoperative cognitive dysfunction in rats via the JAK2/STAT3 signaling pathway

Sun

Jin

et al. 2019

Int J Mol Med

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Postoperative cognitive dysfunction (POCD) is a common and well-known complication following surgery, particularly cardiopulmonary bypass (CPB) surgery. There are currently no suitable treatments for POCD, which is associated with increased illness and mortality rates. The present study aimed to identify a novel treatment for POCD. The protective effect of kappa opioid receptor (KOR) agonists on POCD in rats following CPB was determined and the regulatory mechanism of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was examined. The rats were randomly divided into five groups: Sham operation (Sham group), CPB operation (CPB group), KOR agonist + CPB (K group), KOR agonist + norbinaltorphimine (nor-BNI) + CPB (NK group), and KOR agonist + JAK2-STAT3 specific pathway inhibitor + CPB (AG group). A water maze test and neurological function scores were used to evaluate POCD. Hematoxylin and eosin staining was used to observe hippocampal neurons. ELISA was used to detect the levels of inflammatory factors, oxidative stress factors and brain injury markers. Immunofluorescence was used to visualize the neurons. TUNEL staining and western blotting were used to detect neuronal apoptosis, and western blotting was also used to detect JAK2/STAT3 pathway-related proteins. The KOR agonists significantly improved POCD. S-100β and NSE detection revealed that KOR agonists alleviated brain damage in CPB rats, and this result was reversed by KOR antagonists. The KOR agonists led to a significantly reduced inflammatory response and oxidative stress, as determined by ELISA detection, and attenuated hippocampal neuronal apoptosis, as revealed by TUNEL staining and western blotting, compared with the results in the CPB group. Finally, the KOR agonists inhibited the expression levels of phosphorylated (p-)JAK2 and p-STAT3, rather than total JAK2 and STAT3, compared with levels in the CPB group. Taken together, KOR agonists improved POCD in rats with CPB by inhibiting the JAK2/STAT3 signaling pathway.

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2-Arachidonylglycerol Protects Primary Astrocytes Exposed to Oxygen-Glucose Deprivation Through a Blockade of NDRG2 Signaling and STAT3 Phosphorylation

Cited by 10 publications

References 37 publications

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Kappa opioid receptor agonists improve postoperative cognitive dysfunction in rats via the JAK2/STAT3 signaling pathway

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