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Purification and Primary Culture of Type II Pneumocytes and Their Application in the Study of Pulmonary Metabolism
Published in Joan Gil, Models of Lung Disease, 2020
Type II pneumocytes have been studied in some pathological conditions. After acute exposure to bleomycin, the isolated type II cells were hypertrophic and possessed an increased capacity to synthesize surfactant lipids (Kikkawa et al., 1976). Wright et al. (1982) studied the changes of type II cell lipid metabolism after exposure to NO2. A general increase in cell content of biosynthetic enzyme activities (units/mg DNA) was observed in type II cells from NO2-exposed rats, but no change was detected in the activity of the microsomal marker enzyme, NADPH cytochrome c reductase. Glycerolphosphate acyltransferase and choline phosphotransferase increased 171 and 168%, respectively, and phosphatidate phosphohydrolase increased 69%. Glycerolphosphate phosphatidyltransferase increased 143% and succinate cytochrome c reductase, the mitochondrial marker enzyme, increased 111%. The increases in protein content and activity of phospholipid biosynthetic enzymes in type II cells are consistent with a general hypertrophy of type II cells, which includes stimulation of surfactant phospholipid biosynthesis 2 days after exposure to NO2 when type II cell proliferation is occurring.
Mucolipidosis II and III/ (I-cell disease and pseudo-Hurler polydystrophy) N-acetyl-glucosaminyl-l-phosphotransferase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Mucolipidosis II and III reflect multiple deficiencies of many lysosomal hydrolases that require post-translational processing to form the recognition site that permits their cellular uptake. The fundamental defect is in N-acetylglucosaminyl-l-phosphotransferase (GlcNAc phosphotransferase) (Figure 83.2) [1]. The lysosomal enzyme substrates for this enzyme are glycoproteins containing reactive mannose molecules, and in the reaction a GlcNAc phosphate is linked to the mannose; a subsequent phosphodiesterase reaction cleaves off the GlcNAc, leaving the mannose phosphate recognition site. Patients with I-cell disease, or mucolipidosis II, have complete deficiency of this enzyme, while patients with mucolipidosis III have varying amounts of residual activity of the enzyme. Variable patterns of clinical phenotype in mucolipidosis III reflect the considerable variation in enzyme activity as well as its effect on so very many lysosomal enzymes. The extent of the phenotypic variability has doubtless not yet been defined. Leroy and colleagues [2, 3] gave the disease its name I-cell disease, the I indicating inclusions.
Cytomegalovirus
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
Ganciclovir is a nucleoside analogue drug with antiviral activity against sensitive strains of CMV [102]. For activity, the drug must be phosphorylated by a CMV phosphotransferase enzyme encoded by the UL97 gene. The phosphotransferase converts ganciclovir to ganciclovir monophosphate, which in turn is phosphorylated to ganciclovir triphosphate by cellular enzymes. The triphosphate form exerts antiviral activity via inhibition of the DNA polymerase enzyme, by interfering with elongation of viral DNA. Because of the critical role of the phosphotransferase, mutations in the UL97 gene result in ganciclovir resistance [103]. These resistant CMV isolates have been reported in a variety of patient populations, especially in individuals who have received prolonged antiviral therapy. Ganciclovir resistance can also occur in strains with mutations in the CMV DNA polymerase gene.
Nicotinamide could reduce growth and cariogenic virulence of Streptococcus mutans
Published in Journal of Oral Microbiology, 2022
Yongwang Lin, Tao Gong, Qizhao Ma, Meiling Jing, Ting Zheng, Jiangchuan Yan, Jiamin Chen, Yangyang Pan, Qun Sun, Xuedong Zhou, Yuqing Li
We further conducted gene annotation enrichment of DEGs using the DAVID bioinformatics tools (http://david.abcc.ncifcrf. gov/) to gain insights into the biological effects of NAM on S. mutans. As shown in Figure 3b, the DEGs were enriched in six pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG), with seven gene ontology (GO) terms. Notably, the integral component of membrane, sugar metabolism, the phosphotransferase system, and microbial metabolism in diverse environments were enriched with downregulated genes. In contrast, GO terms, including damaged DNA binding, the arginine biosynthesis process, and the KEGG pathways, including oxocarboxylic acid metabolism and arginine biosynthesis, were significantly enriched with upregulated genes (Figure 3b, P< 0.05).
Proteomic response in Streptococcus gordonii DL1 biofilm cells during attachment to salivary MUC5B
Published in Journal of Oral Microbiology, 2021
Carolina Robertsson, Gunnel Svensäter, Zoltan Blum, Magnus E Jakobsson, Claes Wickström
Also, among the novel biofilm cell proteins was the multiple-sugar metabolism transmembrane permease F (MsmF), a transmembrane helical protein [27]. Based on reduced uptake and fermentation of a variety of carbohydrates in an MsmF-mutant, S. mutans MsmF was confirmed to be involved in the low-affinity multiple-sugar metabolism (msm) [36]. Several mono- and disaccharides have been identified as substrates for the msm system in S. mutans [37]. A phosphotransferase system (PTS) deficient mutant of S. mutans was found to switch to msm, which in turn reduced the total carbohydrate transport and metabolism in the cells [38]. A shift towards the low-affinity msm system may benefit biofilm lifestyle cells by reducing the flow through the central carbon metabolism and thereby protecting the biofilm against harmful acidification.
Neochlorogenic acid: an anti-HIV active compound identified by screening of Cortex Mori [Morus Alba L. (Moraceae)]
Published in Pharmaceutical Biology, 2021
Jing Li, Lu Dou, Shuangfeng Chen, Honghao Zhou, Fangzheng Mou
The PubChem ID of neochlorogenic acid is 5280633, the molecular formula is C16H18O9, and the molecular weight is 354.31 g/mol. A total of 58 protein targets with neochlorogenic acid (normalised fit score > 0.7) were obtained. GO enrichment analysis revealed that these targets mainly involve cellular reactions (such as cellular response to lipid and response to inorganic substance), synthetic or metabolic processes (such as aromatic compound catabolic process, carboxylic acid biosynthetic process, and other biological processes), and molecular functions (such as phosphotransferase activity, hydrolase activity, oxidoreductase activity, and protein domain specific binding) (Figure 7(A)). The pathway analysis showed that the main pathways were prostate cancer, oestrogen signalling pathway, nitrogen metabolism, and other signalling pathways (Figure 7(B)). With PPI analysis, after removal of outliers, a PPI network with 40 nodes and 82 edges was obtained, with an average node degree of 4.2; the largest node degrees were for EGFR, ESR1, and AR (node degrees of 18, 14, and 11, respectively) (Figure 7(C)).