Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts

Asfaw, Befekadu; Schindler, Detlev; Ledvinová, Jana; Černý, Bohuslav; Šmíd, F.; Conzelmann, Ernst

doi:10.1016/s0022-2275(20)32164-7

Cited by 15 publications

(6 citation statements)

References 36 publications

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“…Two downregulated proteins, Ig heavy variable 5-10-1 and alpha-N-acetylgalactosaminidase, were also found in aqueous changes in patients with iERM. Alpha-Nacetylgalactosaminidase is an isoenzyme of alphagalactosidases that functions in the lysosome [50] and is related to Schindler disease [51] and Kanzaki disease [52] with variable neuroaxonal dystrophy and neurological signs. Therefore, we considered lysosome function to be involved in the iERM formation process.…”

Section: Discussionmentioning

confidence: 99%

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

et al. 2022

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Idiopathic epiretinal membrane (iERM) is a pathological fibrocellular change in the vitreoretinal junction over the macular area; however, possible pathogenic mechanisms remain unclear. Changes in the differential protein composition of the aqueous humor (AH) may represent potential molecular changes associated with iERM. To gain new insights into the molecular mechanisms of iERM pathology, a sensitive label-free proteomics analysis was performed to compare AH protein expressions in patients with cataracts with or without iERM. This study employed nanoflow ultra-high-performance liquid chromatography-tandem mass spectrometry to investigate protein compositions of the AH obtained from individual human cataract eyes from 10 patients with iERM and 10 age-matched controls without iERM. Eight proteins were differentially expressed between the iERM and control samples, among which six proteins were upregulated and two were downregulated. A gene ontology (GO) analysis revealed that iERM was closely associated with several biological processes, such as immunity interactions, cell proliferation, and extracellular matrix remodeling. Additionally, multiple proteins, including lumican, cyclin-dependent kinase 13, and collagen alpha-3(VI) chain, were correlated with the central retinal thickness, indicating a multifactorial response in the pathogenic process of iERM. Changes in the AH level of lumican between iERM and control samples were also confirmed by an enzyme-linked immunosorbent assay. In conclusion, several pathological pathways involved in iERM were identified in the AH by a proteomic analysis, including immune reactions, cell proliferation, and remodeling of the extracellular matrix. Lumican is a potential aqueous biomarker for predicting iERM development and monitoring its progression. More clinical parameters also need to be identified to complete the analysis, and those could provide additional targets for treating and preventing iERM.

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Section: Discussionmentioning

confidence: 99%

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

et al. 2022

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“…Briefly, cell pellets were reconstituted in 250 μl of MilliQ water and homogenized by ultrasound using a Digital Sonifier Model 450 (Branson Ultrasonics Corporation, Danbury, Connecticut). Protein concentration was analyzed by Bradford assay and a modified Folch method was used for lipid extraction 20 . Briefly, lipids were extracted from 200 μl homogenates after addition of 800 μl of chloroform:methanol (2:1; vol/vol).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were processed as previously described. 20 Briefly, cell pellets were reconstituted in 250 μl of MilliQ water and homogenized by ultrasound using a Digital Sonifier Model 450 (Branson Ultrasonics Corporation, Danbury, Connecticut). Protein concentration was analyzed by Bradford assay and a modified Folch method was used for lipid extraction.…”

Section: Methodsmentioning

confidence: 99%

“…Protein concentration was analyzed by Bradford assay and a modified Folch method was used for lipid extraction. 20 Briefly, lipids were extracted from 200 μl homogenates after addition of 800 μl of chloroform:methanol (2:1; vol/vol). Upper and lower liquid phases, were separated from the protein precipitate, combined, and evaporated under a stream of nitrogen.…”

Section: Methodsmentioning

confidence: 99%

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Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency

Rybová

Kuchař

Sikora

et al. 2022

J of Inher Metab Disea

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Acid ceramidase catalyzes the degradation of ceramide into sphingosine and a free fatty acid. Acid ceramidase deficiency results in lipid accumulation in many tissues and leads to the development of Farber disease (FD). Typical manifestations of classical FD include formation of subcutaneous nodules and joint contractures as well as the development of a hoarse voice. Healthy skin depends on a unique lipid profile to form a barrier that confers protection from pathogens, prevents excessive water loss, and mediates cell-cell communication. Ceramides comprise $50% of total epidermis lipids and regulate cutaneous homeostasis and inflammation. Abnormal skin development including visual skin lesions has been reported in FD patients, but a detailed study of FD skin has not been performed. We conducted a pathophysiological study of the skin in our mouse model of FD. We observed altered lipid composition in FD skin dominated by accumulation of all studied ceramide species and buildup of abnormal storage structures affecting mainly the dermis. A deficiency of acid ceramidase activity also led to the activation of inflammatory IL-6/JAK/signal transducer and activator of transcription 3 and noncanonical NF-κB signaling pathways. Last, we report reduced proliferation of FD mouse fibroblasts and adipose-derived stem/stromal cells (ASC) along with impaired differentiation of ASCs into mature adipocytes.

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“…In our journey to find the possible mechanism, through which USP35 exerts its role in CRC, we identified α-L-fucosidase 1 (FUCA1) as a potential target. FUCA1 is an enzyme that hydrolyzes terminal fucose residues from glycolipids or glycoproteins [25,26], and its function in cancers remains obscure and controversial. While a few studies suggest that FUCA1 restrains tumor growth, attenuates cell motility, triggers cell death, and sensitizes cancer cells to chemotherapy [27][28][29], two other studies lead to quite opposite conclusions [30,31].…”

Section: Introductionmentioning

confidence: 99%

USP35 promotes cell proliferation and chemotherapeutic resistance through stabilizing FUCA1 in colorectal cancer

et al. 2023

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Ubiquitin-specific-processing proteases 35 (USP35) is an under-characterized deubiquitinase and its role in colorectal cancer (CRC) remains unclear. Here, we focus on delineating the impact of USP35 on CRC cell proliferation and chemo-resistance, as well as the possible regulatory mechanism. By examining the genomic database and clinical samples, we found that USP35 was overexpressed in CRC. Further functional studies showed that enhanced USP35 expression promoted CRC cell proliferation and resistance to oxaliplatin (OXA) and 5-fluorouracil (5-FU), whereas USP35 depletion impeded cell proliferation and sensitized cells to OXA and 5-FU treatments. Then, to explore the possible mechanism underlying USP35-triggered cellular responses, we performed co-immunoprecipitation (co-IP) followed by mass spectrometry (MS) analysis and identified α-L-fucosidase 1 (FUCA1) as a direct deubiquitiation target of USP35. Importantly, we demonstrated that FUCA1 was an essential mediator for USP35-induced cell proliferation and chemo-resistance in vitro and in vivo. Finally, we observed that nucleotide excision repair (NER) components (e.g., XPC, XPA, ERCC1) were up-regulated by USP35-FUCA1 axis, indicating a potential mechanism for USP35-FUCA1-mediated platinum resistance in CRC. Together, our results for the first time explored the role and important mechanism of USP35 in CRC cell proliferation and chemotherapeutic response, providing a rationale for USP35-FUCA1-targeted therapy in CRC.

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Degradation of blood group A glycolipid A-6-2 by normal and mutant human skin fibroblasts

Cited by 15 publications

References 36 publications

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study

Skin inflammation and impaired adipogenesis in a mouse model of acid ceramidase deficiency

USP35 promotes cell proliferation and chemotherapeutic resistance through stabilizing FUCA1 in colorectal cancer

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