Leishmania donovani infection induce Extracellular signal-regulated kinase ½ (ERK½) mediated lipid droplet generation in macrophages

2022 ◽  
Vol 141 ◽  
pp. 328-337
Author(s):  
Somenath Banerjee ◽  
Dipayan Bose ◽  
Subhadip Das ◽  
Nabanita Chatterjee ◽  
Snehasish Mishra ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Leishmania Donovani ◽  
Droplet Generation ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

scholarly journals Leishmania donovani Suppresses Activated Protein 1 and NF-κB Activation in Host Macrophages via Ceramide Generation: Involvement of Extracellular Signal-Regulated Kinase

2002 ◽  
Vol 70 (12) ◽  
pp. 6828-6838 ◽  
Author(s):  
Sanjukta Ghosh ◽  
Sandip Bhattacharyya ◽  
Madhumita Sirkar ◽  
Gouri Shankar Sa ◽  
Tanya Das ◽  
...  
Keyword(s):  
Dna Binding ◽  
Leishmania Donovani ◽  
Fumonisin B1 ◽  
Parasite Burden ◽  
Mitogen Activated Protein Kinase ◽  
Ceramide Level ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Ceramide Synthesis

ABSTRACT In vitro infection of murine peritoneal macrophages with the protozoan Leishmania donovani has been found to alter the signaling parameters of the host. The present study indicates that the enhancement of intracellular ceramide level in macrophages after infection is a major event relating to macrophage dysfunction. We have previously demonstrated that increased ceramide synthesis in host macrophages was involved in the dephosphorylation of extracellular signal-regulated kinase (ERK). In the present study, we further show that downregulation of ERK by ceramide was found to be associated with the inhibition of activated protein 1 (AP-1) and NF-κB transactivation. Pharmacological inhibition of ceramide synthesis by Fumonisin B1 restored the induction of AP-1 and NF-κB DNA-binding activities in infected BALB/c macrophages. On the contrary, in the case of macrophages from the leishmaniasis-resistant C.D2 mice, L. donovani failed to induce sustained ceramide synthesis. Enhanced mitogen-activated protein kinase phosphorylation, AP-1 and NF-κB DNA-binding activity, and the generation of nitric oxide (NO) were observed in L. donovani-infected C.D2 macrophages. ERK activation was necessary for the activation of transcription factors AP-1 and NF-κB, NO generation, and restriction of the parasite burden in the resistant murine host macrophages. Hence, the induction of ceramide synthesis in host macrophages appears to be instrumental and one of the turning points leading to silencing of the macrophage antileishmanial responses.

Overexpression of p62 Induces Autophagy and Promotes Proliferation, Migration and Invasion of Nasopharyngeal Carcinoma Cells through Promoting ERK Signaling Pathway

2020 ◽  
Vol 20 (8) ◽  
pp. 624-637 ◽  
Author(s):  
Qiong Wu ◽  
Manlin Xiang ◽  
Kun Wang ◽  
Zhen Chen ◽  
Lu Long ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Clinical Analysis ◽  
Carcinoma Cells ◽  
Immunofluorescent Staining ◽  
Clinicopathological Parameters ◽  
Migration And Invasion ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Potential Biomarker

Background: Increasing evidence has shown that p62 plays an important role in tumorigenesis. However, relatively little is known about the association between p62 and tumor invasion and metastasis; in addition, its role in NPC (nasopharyngeal carcinoma, NPC) has been rarely investigated. Objective: To investigate the effect of p62 on tumorigenesis and metastasis in nasopharyngeal carcinoma. Methods: Western blotting, immunofluorescent staining and immunohistochemistry were used to evaluate p62 protein expression. Subsequently, cell viability, colony formation, migration, invasion and autophagy assays were performed. anti-p62 autoantibodies in sera were detected by ELISA. These data were correlated with clinicopathological parameters. Results: We confirmed that p62 was significantly up-regulated in NPC tissues. Furthermore, high expression of p62 was observed in NPC cell lines, and especially in the highly metastatic 5-8F cells. In vitro, down-regulation of p62 inhibited proliferation, clone forming ability, autophagy, migration, and invasion in 5-8F cells, whereas p62 overexpression resulted in the opposite effects in 6-10B cells. Moreover, we confirmed that p62 promotes NPC cell proliferation, migration, and invasion by activating ERK (extracellular signal-regulated kinase, ERK). Clinical analysis indicated that high p62 expression correlates with lymph node and distant metastasis (P<0.05). Serum anti-p62 autoantibodies were increased in NPC patients and levels were associated with metastasis. Conclusion : Our data establish p62 targeting ERK as potential determinant in the NPC, which supplies a new pathway to treat NPC. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis and metastasis in NPC.

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