Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway

Zhang, Jie; Li, Yiyi; Wang, Chao; Wang, Yaya; Zhang, Yangyang; Huang, Liqin; Zhang, Zhaohui

doi:10.3389/fnmol.2020.00016

Cited by 18 publications

(19 citation statements)

References 31 publications

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“…MAPK pathways, such as ERK1/2, p38, and c-Jun N-terminal kinase (JNK), are known to participate in NLRP3 inflammasome by upregulating NLRP3 [ 29 , 30 , 31 ]. These pathways are effector ones of LPA 1 [ 32 ]. Therefore, the LPA/LPA 1 signaling axis might regulate NLRP3 upregulation by activating MAPKs.…”

Section: Resultsmentioning

confidence: 99%

“…All these signaling pathways can influence NLRP3 inflammasome activation as players for the priming signal to induce NLRP3 upregulation [ 26 , 27 , 29 , 30 , 31 ]. They are also well-known as effector pathways after LPA 1 activation [ 32 ]. Indeed, the current in vitro study clearly showed that suppressing LPA 1 activity by AM152 treatment attenuated the activation of NF-κB, ERK1/2, and p38 in LPS-primed BMDMs following LPA exposure.…”

Section: Discussionmentioning

confidence: 99%

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NLRP3 Inflammasome Activation Is Involved in LPA1-Mediated Brain Injury after Transient Focal Cerebral Ischemia

Lee

Sapkota

Gaire

et al. 2020

IJMS

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Lysophosphatidic acid receptor 1 (LPA1) contributes to brain injury following transient focal cerebral ischemia. However, the mechanism remains unclear. Here, we investigated whether nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation might be an underlying mechanism involved in the pathogenesis of brain injury associated with LPA1 following ischemic challenge with transient middle cerebral artery occlusion (tMCAO). Suppressing LPA1 activity by its antagonist attenuated NLRP3 upregulation in the penumbra and ischemic core regions, particularly in ionized calcium-binding adapter molecule 1 (Iba1)-expressing cells like macrophages of mouse after tMCAO challenge. It also suppressed NLRP3 inflammasome activation, such as caspase-1 activation, interleukin 1β (IL-1β) maturation, and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation, in a post-ischemic brain. The role of LPA1 in NLRP3 inflammasome activation was confirmed in vitro using lipopolysaccharide-primed bone marrow-derived macrophages, followed by LPA exposure. Suppressing LPA1 activity by either pharmacological antagonism or genetic knockdown attenuated NLRP3 upregulation, caspase-1 activation, IL-1β maturation, and IL-1β secretion in these cells. Furthermore, nuclear factor-κB (NF-κB), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 were found to be LPA1-dependent effector pathways in these cells. Collectively, results of the current study first demonstrate that LPA1 could contribute to ischemic brain injury by activating NLRP3 inflammasome with underlying effector mechanisms.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NLRP3 Inflammasome Activation Is Involved in LPA1-Mediated Brain Injury after Transient Focal Cerebral Ischemia

Lee

Sapkota

Gaire

et al. 2020

IJMS

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“…It was reported that baicalein could activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in MCAO rats [66]. Besides, formononetin mediated neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway [67]. MAPK signaling pathways may be a therapeutic targets for stroke [68].…”

Section: Discussionmentioning

confidence: 98%

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Buyang Huanwu Decoction in the treatment of Ischemic Stroke

Gao

Tian

Han

et al. 2020

Preprint

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Background and objective: With the exact clinical efficacy, Buyang Huanwu decoction (BHD) is a classical prescription for the treatment of ischemic stroke (IS). Here, we aimed to investigate the pharmacological mechanisms of BHD in treating IS using systems biology approaches.Methods: The bioactive components and potential targets of BHD were screened by TCMSP, BATMAN-TCM, ETCM, and SymMap databases. Besides, compounds that failed to find the targets from the above databases were predicted through STITCH, SWISS, and SEA. Moreover, six databases were searched to mine targets of IS. The intersection targets were obtained, and analyzed by GO and KEGG enrichment. Furthermore, BHD-IS PPI network, compound-compound target-IS network and pathway of drug-compound target-IS network were constructed by Cytoscape 3.6.0. Finally, AutoDock was used for molecular docking verification.Results：A total of 253 putative targets were obtained from 60 active compounds in BHD. Among them, 62 targets were related to IS. PPI network showed that the top ten key targets were IL6, TNF, VEGFA, and AKT1, etc. The enrichment analysis demonstrated candidate BHD targets were more frequently involved TNF, PI3K-Akt, and NF-kappa B signaling pathway. Network topology analysis showed that Radix Astragali was the main herb in BHD, and the key components were quercetin, beta-Sitosterol, kaempferol, and stigmasterol, etc. The results of molecular docking showed the active components in BHD had a good binding ability with the key targets.Conclusions: This study firstly adopted the methods of network pharmacology and molecular docking to reveal the relationships among herbs in BHD, the putative targets and IS-related pathways.

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“…Besides, formononetin mediated neuroprotection against cerebral ischemia/reperfusion in rats via downregulation of the Bax/Bcl-2 ratio and upregulation PI3K/Akt signaling pathway [ 66 ]. The MAPK signaling pathway may be a therapeutic pathway for stroke [ 67 ]. Researches showed that suppressing the NF- κ B and MAPK signaling pathways would downregulate the expression of proinflammatory factors.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Buyang Huanwu Decoction in the Treatment of Ischemic Stroke

Gao

Tian

Han

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background and Objective. With the exact clinical efficacy, Buyang Huanwu decoction (BHD) is a classical prescription for the treatment of ischemic stroke (IS). Here, we aimed to investigate the pharmacological mechanisms of BHD in treating IS using systems biology approaches. Methods. The bioactive components and potential targets of BHD were screened by TCMSP, BATMAN-TCM, ETCM, and SymMap databases. Besides, compounds that failed to find the targets from the above databases were predicted through STITCH, SwissTargetPrediction, and SEA. Moreover, six databases were searched to mine targets of IS. The intersection targets were obtained and analyzed by GO and KEGG enrichment. Furthermore, BHD-IS PPI network, compound-target network, and herb-target-pathway network were constructed by Cytoscape 3.6.0. Finally, AutoDock was used for molecular docking verification. Results. A total of 235 putative targets were obtained from 59 active compounds in BHD. Among them, 62 targets were related to IS. PPI network showed that the top ten key targets were IL6, TNF, VEGFA, AKT1, etc. The enrichment analysis demonstrated candidate BHD targets were more frequently involved in TNF, PI3K-Akt, and NF-kappa B signaling pathway. Network topology analysis showed that Radix Astragali was the main herb in BHD, and the key components were quercetin, beta-sitosterol, kaempferol, stigmasterol, etc. The results of molecular docking showed the active components in BHD had a good binding ability with the key targets. Conclusions. Our study demonstrated that BHD exerted the effect of treating IS by regulating multitargets and multichannels with multicomponents through the method of network pharmacology and molecular docking.

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Lysophosphatidic Acid Induces Apoptosis of PC12 Cells Through LPA1 Receptor/LPA2 Receptor/MAPK Signaling Pathway

Cited by 18 publications

References 31 publications

NLRP3 Inflammasome Activation Is Involved in LPA1-Mediated Brain Injury after Transient Focal Cerebral Ischemia

NLRP3 Inflammasome Activation Is Involved in LPA1-Mediated Brain Injury after Transient Focal Cerebral Ischemia

Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Buyang Huanwu Decoction in the treatment of Ischemic Stroke

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Buyang Huanwu Decoction in the Treatment of Ischemic Stroke

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