Bovine papillomavirus E5 oncoprotein upregulates parkin-dependent mitophagy in urothelial cells of cattle with spontaneous papillomavirus infection: a mechanistic study

This study aimed to provide mechanistic insights into mitophagy pathway associated with papillomavirus infection in urothelial cells of cattle. The elimination of mitochondria via autophagy, termed mitophagy, is an evolutionarily conserved mechanism for mitochondrial quality control and homeostasis. PINK1/parkin-mediated mitophagy, a ubiquitin-dependent selective autophagy of dysfunctional mitochondria, has been described here, for the first time, in urothelial cells from 25 bladder cancers in cattle infected by bovine papillomavirus (BPV). The expression of BPV-2 and BPV-13 E5 oncoprotein was detected by RT-PCR. Abnormal mitochondria delimited by expanding phagophores, were peculiar ultrastructural features of neoplastic urothelial cells. High levels of mitochondrial phosphorylated PINK1/parkin were observed in neoplastic urothelial cells infected by BPVs. Phosphoparkin interacted with mitofusin 2 (Mfn2) and ubiquitin (Ub), which confirmed that Mfn2 is a parkin receptor at the mitochondrial level, where parkin interacted also with Ub. Furthermore, parkin established a complex that was comprised of optineurin, p62, LC3, laforin, and embryonic stem cell-expressed Ras (ERAS), that interacted with BPV E5 oncoprotein, and Bag3, which, in turn, regulated the formation of a complex composed of Hpc70/Hsp70, CHIP, an HSC70-interacting E3 ubiquitin ligase. It is conceivable that ERAS is involved in mitophagosome maturation via phosphatidylinositol 3-kinase (PI3K) pathway. Bag3, in ass...
Source: Comparative Immunology, Microbiology and Infectious Diseases - Category: Infectious Diseases Source Type: research

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Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: 3T3-L1 cells, treated with LPV/RTV, show altered lipid content due to increased miRNA-218 levels, which affects lipin-1 mRNA. Moreover, increased miRNA-218 levels were inversely correlated with changes in GLUT-4 expression, which suggests a role for miRNA-218 in mediating the insulin resistance consequent to cART. Introduction Metabolic syndrome is a serious consequence of combined Antiretroviral Therapy (cART). HIV-associated metabolic syndrome is often accompanied by lipodystrophy (LS), the redistribution of body fat with loss of subcutaneous adipose tissue in face, limbs and buttocks, concomitant wit...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion The elucidation of the function of circRNAs is an emerging field of science with a tremendous potential after previously being dismissed as RNA artifacts. They are ubiquitously expressed and thousands of members have already been identified. This fact only expands their potential to possibly enhance our knowledge to understand the difference between health and disease. Owing to their structure stability and their presence in exosomes circRNAs may also exert their function in an autocrine, paracrine and possible endocrine fashion. In addition, the fact that circRNAs are widely distributed in the cellular compart...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Segun Fatumo1,2,3*, Tommy Carstensen4, Oyekanmi Nashiru3, Deepti Gurdasani4†, Manjinder Sandhu4,5† and Pontiano Kaleebu1,2† 1Uganda Medical Informatics Centre, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda 2London School of Hygiene and Tropical Medicine, London, United Kingdom 3H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria 4Human Genetics, Wellcome Sanger Institute, Hinxton, Cambridge, United Kingdom 5Division of Computational Medicine, Department of Medicine, University of Cambridge, Cambridge, United Kin...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Junhui Zhang1,2†, Lingfei Li1,2†, Qiong Zhang1,2, Xu Yang3, Can Zhang4, Xingyue Zhang1,2, Dongxia Zhang1,2, Yanling Lv1,2, Huapei Song1,2, Bing Chen5, Yao Liu6, Jiongyu Hu2,5*† and Yuesheng Huang1,2*† 1Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China 2State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China 3Department of Respiratory Medicine, The 983 Hospital of Joint Logistics Support Force of the Chinese Peopl...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Xiaohui Xu, Congmin Ma, Zhihui Duan, Yanjiao Du and Chao Liu* Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China Oxidized-low density lipoprotein (ox-LDL) can induce injury of endothelial cells, causing atherosclerosis, which is an important initial event in several cardiovascular diseases. Long non-coding RNAs (lncRNAs) have emerged as regulators of diverse biological processes, but their specific biological functions and biochemical mechanisms in ox-LDL-induced endothelial cell injury have not been well investigated. Here, we describe the initial functional an...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, we found that senescent chondrocytes isolated from OA patients secrete more EVs compared with nonsenescent chondrocytes. These EVs inhibit cartilage ECM deposition by healthy chondrocytes and can induce a senescent state in nearby cells. We profiled the miR and protein content of EVs isolated from the synovial fluid of OA joints from mice with SnCs. After treatment with a molecule to remove SnCs, termed a senolytic, the composition of EV-associated miR and protein was markedly altered. The senolytic reduced OA development and enhanced chondrogenesis, and these were attributable to several specific differenti...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, NC-LAP demonstrate antitumoral effect in HER-positive bladder cells by inducing cell cycle arrest and apoptosis exhibiting better effects compared to the non-encapsulated lapatinib. Our work suggests that the LAP loaded in nanoformulations could be a promising approach to treat tumors that presents EGFR overexpression phenotype. Introduction Bladder cancer (BC) is a heterogeneous disease which presents several molecular characteristics associated with different clinical outcomes (1). Urothelial or transitional cell carcinoma (TCC) represent the most frequent type of bladder cancer (2) and are classifie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: According to the results, we found that lncRNA RMRP was closely related to the progression of bladder cancer, which could be a potential target for treating BC patients. PMID: 30779067 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
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