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World Journal of Gastroenterology Jan 2019Hepatocellular carcinoma (HCC) is the fifth most common cancer, and hepatitis C virus (HCV) infection plays a major role in HCC development. The molecular mechanisms by... (Review)
Review
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and hepatitis C virus (HCV) infection plays a major role in HCC development. The molecular mechanisms by which HCV infection leads to HCC are varied. HCV core protein is an important risk factor in HCV-associated liver pathogenesis and can modulate several signaling pathways involved in cell cycle regulation, cell growth promotion, cell proliferation, apoptosis, oxidative stress and lipid metabolism. The dysregulation of signaling pathways such as transforming growth factor β (TGF-β), vascular endothelial growth factor (VEGF), Wnt/β-catenin (WNT), cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor α (PPARα) by HCV core protein is implicated in the development of HCC. Therefore, it has been suggested that this protein be considered a favorable target for further studies in the development of HCC. In addition, considering the axial role of these signaling pathways in HCC, they are considered druggable targets for cancer therapy. Therefore, using strategies to limit the dysregulation effects of core protein on these signaling pathways seems necessary to prevent HCV-related HCC.
Topics: Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Genome, Viral; Hepacivirus; Humans; Liver; Liver Neoplasms; Signal Transduction; Viral Core Proteins
PubMed: 30643357
DOI: 10.3748/wjg.v25.i1.42 -
Environment International Jan 2023Cigarette butts (CBs), one of the most common litter items found on beaches, represent a still unexplored environmental hazard. This study aimed at a multidisciplinary...
Cigarette butts (CBs), one of the most common litter items found on beaches, represent a still unexplored environmental hazard. This study aimed at a multidisciplinary characterization of their toxicological risks on marine organisms integrating chemical analyses of released compounds with a wide panel of biological responses, such as ecotoxicological bioassays on species of different trophic positions, molecular responses in an ex vivo model (Precision-Cut Tissue Slices, PCTS of mussels digestive glands), bioavailability and cellular biomarkers in mussels exposed to CBs in laboratory experiments. Trace metals, aliphatic and polycyclic aromatic hydrocarbons, nicotine and cotinine were released in artificial seawater after 24 h which determined a significant inhibition of bacterial bioluminescence, oyster embryo development and growth in different algal species. Modulation of peroxisomal proliferation and antioxidant gene expression was observed in mussels PCTS, while the in vivo exposure determined accumulation of chemicals and significant alterations of immune system, antioxidant and neurotoxic responses, peroxisomal proliferation and genotoxic damage. Using a quantitative Weight of Evidence model, the risks of CBs to the marine environment were summarized, highlighting the importance of integrating chemical analyses, batteries of ecotoxicological bioassays, molecular and cellular biomarkers to assess the impact of these hazardous materials on marine environment.
Topics: Animals; Aquatic Organisms; Antioxidants; Water Pollutants, Chemical; Tobacco Products; Bivalvia; Biomarkers; Environmental Monitoring
PubMed: 36628858
DOI: 10.1016/j.envint.2023.107733 -
Cells Feb 2024proliferates by budding, which includes the formation of a cytoplasmic protrusion called the 'bud', into which DNA, RNA, proteins, organelles, and other materials are... (Review)
Review
proliferates by budding, which includes the formation of a cytoplasmic protrusion called the 'bud', into which DNA, RNA, proteins, organelles, and other materials are transported. The transport of organelles into the growing bud must be strictly regulated for the proper inheritance of organelles by daughter cells. In yeast, the RING-type E3 ubiquitin ligases, Dma1 and Dma2, are involved in the proper inheritance of mitochondria, vacuoles, and presumably peroxisomes. These organelles are transported along actin filaments toward the tip of the growing bud by the myosin motor protein, Myo2. During organelle transport, organelle-specific adaptor proteins, namely Mmr1, Vac17, and Inp2 for mitochondria, vacuoles, and peroxisomes, respectively, bridge the organelles and myosin. After reaching the bud, the adaptor proteins are ubiquitinated by the E3 ubiquitin ligases and degraded by the proteasome. Targeted degradation of the adaptor proteins is necessary to unload vacuoles, mitochondria, and peroxisomes from the actin-myosin machinery. Impairment of the ubiquitination of adaptor proteins results in the failure of organelle release from myosin, which, in turn, leads to abnormal dynamics, morphology, and function of the inherited organelles, indicating the significance of proper organelle unloading from myosin. Herein, we summarize the role and regulation of E3 ubiquitin ligases during organelle inheritance in yeast.
Topics: Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Ubiquitin-Protein Ligases; Peroxisomes; Myosins; Ubiquitins; Cell Cycle Proteins; Mitochondrial Proteins
PubMed: 38391905
DOI: 10.3390/cells13040292 -
Experimental and Therapeutic Medicine Apr 2022Osteoporosis (OP) is a systemic metabolic bone disease that occurs most frequently in the elderly. The main pathogenesis of OP is excessive proliferation and...
Osteoporosis (OP) is a systemic metabolic bone disease that occurs most frequently in the elderly. The main pathogenesis of OP is excessive proliferation and differentiation of osteoclasts, in which the peroxisome proliferator-activated receptor γ (PPARγ) pathway has a pivotal role. Recently, heat shock protein (HSP)90α has been identified as an important molecular chaperone with PPARγ, which regulates the effect of the PPARγ pathway. The aim of the present study was to investigate the role of HSP90α involved in the regulation of osteoclast formation and the process of osteoporosis. Firstly, the expression of HSP90α in osteoclast differentiation was detected by western blotting , then the effect of HSP90α inhibition on the formation and differentiation of osteoclasts was examined. Furthermore, the nuclear import of PPARγ was also assessed to confirm the synergistic effect of HSP90α. Finally, the inhibitory effect of HSP90α was explored, using a mouse model of osteoporosis. As a result, in the process of osteoclast differentiation and proliferation, the expression of HSP90α was upregulated. Inhibition of HSP90α could block the formation and differentiation of osteoclasts, and remit osteoporosis in mice. Regarding the underlying mechanism, inhibition of HSP90α could block the nuclear import of PPARγ to inhibit osteoclast differentiation and proliferation. In conclusion, these data indicated that the inhibition of HSP90α could block osteoclast formation and remit osteoporosis by reducing the nuclear import of PPARγ.
PubMed: 35251339
DOI: 10.3892/etm.2022.11199 -
International Journal of Molecular... Sep 2021Although peroxisomes play an essential role in viral pathogenesis, and viruses are known to change peroxisome morphology, the role of genotype in the peroxisomal...
Although peroxisomes play an essential role in viral pathogenesis, and viruses are known to change peroxisome morphology, the role of genotype in the peroxisomal response to viruses remains poorly understood. Here, we analyzed the impact of wheat streak mosaic virus (WSMV) on the peroxisome proliferation in the context of pathogen response, redox homeostasis, and yield in two wheat cultivars, Patras and Pamir, in the field trials. We observed greater virus content and yield losses in Pamir than in Patras. Leaf chlorophyll and protein content measured at the beginning of flowering were also more sensitive to WSMV infection in Pamir. Patras responded to the WSMV infection by transcriptional up-regulation of the peroxisome fission genes (), (), and (), greater peroxisome abundance, and activation of pathogenesis-related proteins chitinase, and β-1,3-glucanase. Oppositely, in Pamir, WMSV infection suppressed transcription of peroxisome biogenesis genes and activity of chitinase and β-1,3-glucanase, and did not affect peroxisome abundance. Activity of ROS scavenging enzymes was higher in Patras than in Pamir. Thus, the impact of WMSV on peroxisome proliferation is genotype-specific and peroxisome abundance can be used as a proxy for the magnitude of plant immune response.
Topics: Chitinases; Chlorophyll; Disease Resistance; Glucan 1,3-beta-Glucosidase; Oxidation-Reduction; Peroxidases; Peroxisomes; Phenotype; Plant Diseases; Plant Leaves; Potyviridae; Reactive Oxygen Species; Triticum
PubMed: 34638559
DOI: 10.3390/ijms221910218 -
EXCLI Journal 2023The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathogenesis of atherosclerosis and hypertension. It has been proposed...
The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathogenesis of atherosclerosis and hypertension. It has been proposed and verified that hexahydrocurcumin (HHC), a metabolite form of curcumin, has cardiovascular protective effects. This study examined the effect of HHC on angiotensin II (Ang II)-induced proliferation, migration, and inflammation in rat aortic VSMCs and explored the molecular mechanisms related to the processes. The results showed that HHC significantly suppressed Ang II-induced proliferation, migration, and inflammation in VSMCs. HHC inhibited Ang II-induction of the increase in cyclin D1 and decrease in p21 expression in VSMCs. Moreover, HHC attenuated the generation of reactive oxygen species (ROS), and the expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and matrix metalloproteinases-9 (MMP9) in Ang II-induced VSMCs. The proliferation, migration, inflammation, and ROS production were also inhibited by GKT137831 (NADPH oxidase, NOX1/4 inhibitor) and the combination of HHC and GKT137831. In addition, HHC restored the Ang-II inhibited expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). These findings indicate that HHC may play a protective role in Ang II-promoted proliferation, migration, and inflammation by suppressing NADPH oxidase mediated ROS generation and elevating PPAR-γ and PGC-1α expression. See also Figure 1(Fig. 1).
PubMed: 37534221
DOI: 10.17179/excli2023-6124 -
Cancers Sep 2020Mitochondria are organelles that are mainly involved in the generation of ATP by cellular respiration. In addition, they modulate several intracellular functions,... (Review)
Review
Mitochondria are organelles that are mainly involved in the generation of ATP by cellular respiration. In addition, they modulate several intracellular functions, ranging from cell proliferation and differentiation to cell death. Importantly, mitochondria are social and can interact with other organelles, such as the Endoplasmic Reticulum, lysosomes and peroxisomes. This symbiotic relationship gives advantages to both partners in regulating some of their functions related to several aspects of cell survival, metabolism, sensitivity to cell death and metastasis, which can all finally contribute to tumorigenesis. Moreover, growing evidence indicates that modulation of the length and/or numbers of these contacts, as well as of the distance between the two engaged organelles, impacts both on their function as well as on cellular signaling. In this review, we discuss recent advances in the field of contacts and communication between mitochondria and other intracellular organelles, focusing on how the tuning of mitochondrial function might impact on both the interaction with other organelles as well as on intracellular signaling in cancer development and progression, with a special focus on calcium signaling.
PubMed: 32927611
DOI: 10.3390/cancers12092574 -
Cancer Cell International Feb 2024SLC25A17, a peroxisomal solute carrier, has been implicated in various physiological and pathological processes. However, its precise roles and underlying mechanisms in...
BACKGROUND
SLC25A17, a peroxisomal solute carrier, has been implicated in various physiological and pathological processes. However, its precise roles and underlying mechanisms in triple-negative breast cancer (TNBC) remain incompletely understood.
METHODS
The expression and survival data of breast cancer were derived from TCGA and GEO databases. A variety of in vitro assays were conducted, including proliferation, apoptosis, cell cycle, migration, and invasion. Reactive oxygen species (ROS) were measured by immunofluorescence microscopy and flow cytometry. The levels of autophagy were assessed by mRFP-GFP-LC3 confocal microscopy scanning, western blotting, and electron microscopy.
RESULTS
SLC25A17 was highly expressed in breast cancer tissues, which was found to be associated with unfavorable prognosis. Functional assays demonstrated that SLC25A17 knockdown suppressed proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion. Moreover, it prompted apoptosis and autophagy. On the other hand, SLC25A17 knockdown promoted autophagy through triggering ROS accumulation, which was counteracted by N-acetyl-l-cysteine (NAC). Furthermore, the pro-apoptotic effect of SLC25A17 knockdown was reversed when treated with autophagy inhibitor 3-MA in TNBC cells, suggesting that SLC25A17 knockdown-induced autophagic cell death. Mechanistically, SLC25A17 performed its function through regulation JAK2/STAT3 signaling in TNBC. In a nude mice xenograft study, SLC25A17 knockdown markedly decreased breast tumor growth and metastasis.
CONCLUSION
SLC25A17 up-regulation may be a critical factor driving TNBC progression by modulating ROS production and autophagy. Consequently, targeting SLC25A17 could be an effective therapeutic strategy against TNBC.
PubMed: 38402166
DOI: 10.1186/s12935-024-03270-z -
FEBS Open Bio Dec 2022When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby...
When skeletal muscle is damaged, satellite cells (SCs) are activated to proliferate rapidly and fuse with the damaged muscle fibers to form new muscle fibers, thereby promoting muscle growth and remodeling and repair of trauma. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. Therefore, we hypothesized that, when muscles are injured, myoblast-derived exosomes may regulate muscle repair and regeneration. Here, we investigated the underlying mechanism by applying C2C12-derived exosomes to injured mouse skeletal muscles. The expression levels of skeletal muscle regeneration factors paired box 7 and lipid-promoting factor peroxisome proliferator-activated receptor γ were upregulated, whereas the expression levels of fibrosis factors collagen-1 and α-smooth muscle actin decreased. The expression of proliferating cell nuclear antigen was elevated after applying C2C12-derived exosomes to SCs. Application of C2C12-derived exosomes to fibro-adipogenic progenitors resulted in an increase in peroxisome proliferator-activated receptor γ expression and adipogenesis capacity, whereas α-smooth muscle actin expression and fibrosis capacity decreased. Analysis of the transcriptome and proteome of SCs after treatment with exosomes showed the involvement of multiple biological processes, including proliferation and differentiation of SCs, muscle regeneration, skeletal muscle atrophy, and the inflammatory response after muscle injury. Hence, our data suggest that C2C12-derived exosomes can promote the regeneration of skeletal muscle fibers, accelerate the production of fat from damaged muscles, inhibit the fibrosis of damaged muscles, and accelerate injury repair, which is related to exosome-mediated regulation of the proliferation of SCs, differentiation of fibro-adipogenic progenitors, and modulation of SC mRNA expression and protein formation and decomposition.
Topics: Mice; Humans; Animals; Exosomes; PPAR gamma; Actins; Myoblasts; Muscle, Skeletal; Fibrosis
PubMed: 36325691
DOI: 10.1002/2211-5463.13504 -
PPAR Research 2018Peroxisome proliferator-activated receptor (PPAR) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation,... (Review)
Review
Peroxisome proliferator-activated receptor (PPAR) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPAR coactivator-1 (PGC-1), initially identified as a PPAR-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism and energy homeostasis. The role of PGC-1 in diabetes, neurodegeneration, and cardiovascular disease is particularly well known. PGC-1 is also now known to play important roles in cancer, independent of the role of PPAR in cancer. Though many researchers have studied the expression and clinical implications of PPAR and PGC-1 in cancer, there are still many controversies about the role of PPAR and PGC-1 in cancer. This review examines and summarizes some recent data on the role and action mechanisms of PPAR and PGC-1 in cancer, respectively, particularly the recent progress in understanding the role of PPAR in several cancers since our review was published in 2012.
PubMed: 29599799
DOI: 10.1155/2018/6727421