Role of LncRNA MALAT-1 in hypoxia-induced PC12 cell injury via regulating p38MAPK signaling pathway

The abnormal neurites have long been regarded as the main player contributing to the poor outcome of patients with subarachnoid hemorrhage (SAH). (-)-Eigallocatechin-3-gallate (EGCG), the major biological component of tea catechin, exhibited strong neuroprotective effects against central nervous system diseases; however, the role of EGCG-mediated neurite outgrowth after SAH has not been delineated. Here, the effect of reactive oxygen species (ROS)/integrin β1/FAK/p38 pathway on neurite outgrowth was investigated. As expected, oxyhemoglobin- (OxyHb-) induced excessive ROS level was significantly reduced by EGCG as well as antioxidant N-acetyl-l-cysteine (NAC). Consequently, the expression of integrin β1 was significantly inhibited by EGCG and NAC. Meanwhile, EGCG significantly inhibited the overexpression of phosphorylated FAK and p38 to basal level after SAH. As a result, the abnormal neurites and cell injury were rescued by EGCG, which eventually increased energy generation and neurological score after SAH. These results suggested that EGCG promoted neurite outgrowth after SAH by inhibition of ROS/integrin β1/FAK/p38 signaling pathway. Therefore, EGCG might be a new pharmacological agent that targets neurite outgrowth in SAH therapy.

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Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 cell injury and mitochondrial dysfunction via Nrf2/SIRT3 signaling pathway

Proceedings for Annual Meeting of The Japanese Pharmacological Society ◽

10.1254/jpssuppl.wcp2018.0_po2-1-47 ◽

2018 ◽

Vol WCP2018 (0) ◽

pp. PO2-1-47

Author(s):

Linying Feng ◽

Nana Chen ◽

Fan Xu ◽

Long Long ◽

Jianmei Gao ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Signaling Pathway ◽

Pc12 Cell ◽

Cell Injury ◽

Glucose Deprivation ◽

Oxygen Glucose Deprivation ◽

Icariside Ii

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Role of the p38MAPK signaling pathway in hippocampal neuron autophagy in rats with chronic intermittent hypoxia

Journal of Neurophysiology ◽

10.1152/jn.00240.2021 ◽

2021 ◽

Author(s):

Yuxin He ◽

Zhili Liu ◽

Yinpei Huang ◽

Bing Li

Keyword(s):

Western Blot ◽

Signaling Pathway ◽

Water Maze ◽

Intermittent Hypoxia ◽

Hippocampal Neuron ◽

Morris Water Maze Test ◽

Chronic Intermittent Hypoxia ◽

Maze Test ◽

P38mapk Signaling

This study explored the role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in hippocampal neuron autophagy in rats with chronic intermittent hypoxia (CIH). Sixty-four male Sprague-Dawley rats were randomly divided to normoxic control (CON), CIH (subdivided into groups A, B, and C undergoing intermittent hypoxia for 2, 4, and 6 weeks, respectively), solvent (CIH+Veh), or p38MAPK inhibitor (CIH+SB203580) groups. DMSO and SB203580 were injected intraperitoneally 30 min before hypoxia in CIH+Veh and CIH+SB203580 group rats, respectively. Rat learning and memory were evaluated via the Morris water maze test. Ultrastructural changes in the hippocampal CA1 region autophagic vesicles and neurons were observed under transmission electron and light microscopy. Hippocampal microtubule-associated proteins were detected by western blot. Morris water maze test showed that CIH+SB203580 group rats spent significantly more time on the platform quadrant and crossed the platform more times than CIH+Veh group rats (P < 0.01). HE staining showed greater rat cell damage in the CIH+SB group than in the CIH and CIH+Veh groups. Western blot analysis showed that CIH+SB group rats had significantly lower p-p38MAPK/p38MAPK, LC3I, and p62 expression and higher beclin-1 expression than CIH+Veh group rats (P < 0.01). Electron microscopy showed that CIH+SB203580 group rats had several small hippocampal neuron autophagic vesicles. On immunofluorescence analyses, it showed a higher LC3II expression in CIH+SB203580 group rats than in CIH+Veh group rats (P < 0.01). These results indicate that inhibition of the CIH p38MAPK signaling pathway can activate autophagy and protect hippocampal neurons in rats.

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Role of PI3K/Akt pathway in effect of paeoniflorin against Aβ25-35-induced PC12 cell injury

China Journal of Chinese Materia Medica ◽

10.4268/cjcmm20142027 ◽

2014 ◽

Keyword(s):

Pc12 Cell ◽

Cell Injury ◽

Akt Pathway

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Sema4D Aggravated LPS-Induced Injury via Activation of the MAPK Signaling Pathway in ATDC5 Chondrocytes

BioMed Research International ◽

10.1155/2020/8691534 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Jinlai Lei ◽

Yahui Fu ◽

Yan Zhuang ◽

Kun Zhang

Keyword(s):

Signaling Pathway ◽

Cell Injury ◽

Mapk Pathway ◽

Mapk Signaling ◽

Degenerative Joint Disease ◽

Mapk Signaling Pathway ◽

Joint Disease ◽

Promoting Effect ◽

Bone Injury

Osteoarthritis (OA) is the most common chronic degenerative joint disease, and it remains the main cause of chronic disability in elderly individuals. Sema4D (semaphorin 4D) is involved in the immune system and related to bone injury, osteoporosis, osteoblast differentiation, and rheumatoid arthritis. However, the role of Sema4D in OA remains unclear. Hence, the LPS-stimulated chondrocyte cell injury model was constructed in this study to investigate the role of Sema4D in OA development. The results showed that Sema4D was increased in LPS-treated ATDC5 cells, and the knockdown of Sema4D suppressed the decline of cell viability, the increase of cell apoptosis, and the increase of IL-6, IL-1β, and TNF-α secretion in ATDC5 cells induced by LPS. Meanwhile, Sema4D overexpression aggravated the cell injury triggered by LPS, and inhibiting Plexin B1 partly abolished the effect of Sema4D overexpression on LPS-induced chondrocyte injury. Furthermore, silencing of Sema4D blocked the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. Enhanced Sema4D promoted the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. What is more, inhibiting the MAPK signaling pathway abolished the promoting effect of Sema4D overexpression on LPS-induced chondrocyte injury. Therefore, our study suggested that the knockdown of Sema4D protects ATDC5 cells against LPS-induced injury through inactivation of the MAPK signaling pathway via interacting with Plexin B1.

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MiR-124-3p Suppresses the Dysfunction of High Glucose-Stimulated Endothelial Cells by Targeting G3BP2

Frontiers in Genetics ◽

10.3389/fgene.2021.723625 ◽

2021 ◽

Vol 12 ◽

Author(s):

Haijun Zhao ◽

Yanhui He

Keyword(s):

Endothelial Cells ◽

Signaling Pathway ◽

High Glucose ◽

Cell Injury ◽

Tube Formation ◽

Luciferase Reporter ◽

Diabetic Microangiopathy ◽

Potential Biomarker ◽

P38mapk Signaling

Background: Diabetic retinopathy (DR) is the most important manifestation of diabetic microangiopathy. MicroRNAs (miRNAs), members of non-coding RNAs, have been frequently reported to regulate various diseases including DR. MiR-124-3p is involved in DR based on bioinformatics. The current study aimed to investigate the role of miR-124-3p in high glucose (HG)-treated human retinal microvascular endothelial cells (HRMECs), an in vitro model of DR.Methods: Bioinformatics analysis was applied to reveal the targets downstream miR-124-3p. A series of assays including CCK-8, luciferase reporter, western blot, and tube formation assays were used to explore the function and mechanism of miR-124-3p in HG-stimulated HRMECs.Results: We found out that miR-124-3p was downregulated in HG-stimulated HRMECs. Functionally, miR-124-3p overexpression restrained the HG-induced cell injury of HRMECs. Mechanistically, we predicted 5 potential target mRNAs of miR-124-3p. G3BP stress granule assembly factor 2 (G3BP2) was validated to bind with miR-124-3p. Rescue assays showed that miR-124-3p suppressed cell injury of HG-stimulated HRMECs through G3BP2. In addition, miR-124-3p regulated the p38MAPK signaling pathway by G3BP2, and G3BP2 promoted injury of HG-treated HRMECs through the activation of the p38MAPK signaling pathway.Conclusion: MiR-124-3p suppressed the dysfunctions of HG-treated HRMECs by targeting G3BP2 and activating the p38MAPK signaling. This new discovery provided a potential biomarker for DR treatment.

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MicroRNA-140-5p ameliorates the high glucose-induced apoptosis and inflammation through suppressing TLR4/NF-κB signaling pathway in human renal tubular epithelial cells

Bioscience Reports ◽

10.1042/bsr20192384 ◽

2020 ◽

Vol 40 (3) ◽

Cited By ~ 4

Author(s):

Jie Su ◽

Jian Ren ◽

Haiyan Chen ◽

Bo Liu

Keyword(s):

Signaling Pathway ◽

High Glucose ◽

Cell Injury ◽

Tubular Cell ◽

Renal Tubular Cell ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Induced Apoptosis ◽

Apoptosis And Inflammation

Abstract Hyperglycemia-induced renal tubular cell injury is thought to play a critical role in the pathogenesis of diabetic nephropathy (DN). However, the role of miRNAs in renal tubular cell injury remains to be fully elucidated. The aim of the present study was to investigate the role and mechanisms of miRNAs protecting against high glucose (HG)-induced apoptosis and inflammation in renal tubular cells. First, we analyzed microRNA (miRNA) expression profiles in kidney tissues from DN patients using miRNA microarray. It was observed that miRNA-140-5p (miR-140-5p) was significantly down-regulated in kidney tissues from patients with DN. An inverse correlation between miR-140-5p expression levels with serum proteinuria was observed in DN patients, suggesting miR-140-5p may be involved in the progression of DN. HG-induced injury in HK-2 cells was used to explore the potential role of miR-140-5p in DN. We found that miR-140-5p overexpression improved HG-induced cell injury, as evidenced by the enhancement of cell viability, and inhibition of the activity of caspase-3 and reactive oxygen species (ROS) generation. It was also observed that up-regulation of miR-140-5p suppressed HG induced the expressions of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in HK-2 cells. In addition, TLR4, one of the upstream molecules of NF-κB signaling pathway, was found to be a direct target of miR-140-5p in the HK-2. Moreover, the HG-induced activation of NF-κB signaling pathway was inhibited by miR-140-5p overexpression. These results indicated that miR-140-5p protected HK-2 cells against HG-induced injury through blocking the TLR4/NF-κB pathway, and miR-140-5p may be considered as a potential prognostic biomarker and therapeutic target in the treatment of DN.

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Asymmetric dimethylarginine (ADMA) accelerates renal cell fibrosis under high glucose condition through NOX4/ROS/ERK signaling pathway

Scientific Reports ◽

10.1038/s41598-020-72943-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Isaivani Jayachandran ◽

Saravanakumar Sundararajan ◽

Saravanakumar Venkatesan ◽

Sairaj Paadukaana ◽

Muthuswamy Balasubramanyam ◽

...

Keyword(s):

Signaling Pathway ◽

Kidney Cell ◽

High Glucose ◽

Renal Cell ◽

Asymmetric Dimethylarginine ◽

Cell Injury ◽

High Glucose Condition ◽

Erk Activity ◽

Glucose Condition

Abstract We previously reported that the circulatory level of Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, was increased in diabetic kidney disease patients. However, the mechanism and the role of ADMA in diabetic kidney injury remain unclear. Hence, our principal aim is to investigate the causal role of ADMA in the progression of renal cell fibrosis under high glucose (HG) treatment and to delineate its signaling alterations in kidney cell injury. High Glucose/ADMA significantly increased fibrotic events including cell migration, invasion and proliferation along with fibrotic markers in the renal cells; whereas ADMA inhibition reversed the renal cell fibrosis. To delineate the central role of ADMA induced fibrotic signaling pathway and its downstream signaling, we analysed the expression levels of fibrotic markers, NOX4, ROS and ERK activity by using specific inhibitors and genetic manipulation techniques. ADMA stimulated the ROS generation along with a significant increase in NOX4 and ERK activity. Further, we observed that ADMA activated NOX-4 and ERK are involved in the extracellular matrix proteins accumulation. Also, we observed that ADMA induced ERK1/2 phosphorylation was decreased after NOX4 silencing. Our study mechanistically demonstrates that ADMA is involved in the progression of kidney cell injury under high glucose condition by targeting coordinated complex mechanisms involving the NOX4- ROS-ERK pathway.

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