Comparative study of the effects of gold and silver nanoparticles on the metabolism of human dermal fibroblasts

Abstract The purpose of this article was to explore the effects of gold nanoparticles (GNPs) and silver nanoparticles (SNPs) with different cytotoxicities on human dermal fibroblasts (HDFs) at the metabolic level. First, ∼20 nm of GNPs and SNPs were prepared, and their effects on the proliferation of HDFs were evaluated. Then, a metabolomics technique was used to analyse the effects of GNPs and SNPs on the expression profiles of metabolites in HDFs after 4, 8 and 24 h of treatment. Furthermore, the key metabolites and key metabolic pathways involved in the interaction of GNPs and SNPs with HDFs were identified through expression pattern analysis and metabolic pathway analysis of differentially expressed metabolites and were finally verified by experiments. The results of the cytotoxicity experiments showed that there was no cytotoxicity after the treatment of GNPs for 72 h, while the cytotoxicity of the SNPs reached grade 1 after 72 h. By using metabolomics analysis, 29, 30 and 27 metabolites were shown to be differentially expressed in HDFs after GNP treatment, while SNPs induced the differential expression of 13, 33 and 22 metabolites after 4, 8 and 24 h of treatment, respectively. Six and four candidate key metabolites in the GNP and SNP groups were identified by expression pattern analysis and metabolic pathway analysis, respectively. The key metabolic pathways in the GNP and SNP groups were identified as the glutathione metabolic pathway (the key metabolite of which was glutathione) and the citrate cycle pathway (the key metabolite of which was malic acid). Based on the experiments used to verify the key metabolites and key metabolic pathways, it was found that the increase in glutathione after GNP treatment might trigger an oxidative stress protection mechanism and thus avoid cytotoxicity. After exposure to SNPs, the citric acid content was increased, mainly through the citrate cycle pathway, thereby inhibiting the synthesis of malic acid to affect the formation of ATP and finally leading to cytotoxicity.

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Elementary Mode Analysis: A Useful Metabolic Pathway Analysis Tool for Reprograming Microbial Metabolic Pathways

Subcellular Biochemistry - Reprogramming Microbial Metabolic Pathways ◽

10.1007/978-94-007-5055-5_2 ◽

2012 ◽

pp. 21-42 ◽

Cited By ~ 7

Author(s):

Cong T. Trinh ◽

R. Adam Thompson

Keyword(s):

Pathway Analysis ◽

Metabolic Pathway ◽

Metabolic Pathways ◽

Mode Analysis ◽

Analysis Tool ◽

Elementary Mode ◽

Metabolic Pathway Analysis ◽

Elementary Mode Analysis ◽

Pathway Analysis Tool

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Deciphering Potential Drug Targets in Clostridium Perfringens through Metabolic Pathway Analysis

International Journal of Scientific Research in Science Engineering and Technology ◽

10.32628/ijsrst196163 ◽

2019 ◽

pp. 432-437

Author(s):

M Arockiyajainmary ◽

Sivashankari Selvarajan

Keyword(s):

Clostridium Perfringens ◽

Pathway Analysis ◽

Metabolic Pathway ◽

Metabolic Pathways ◽

Drug Targets ◽

Cellular Localization ◽

Potential Drug ◽

Metabolic Pathway Analysis ◽

Homologous Proteins ◽

Potential Drug Targets

Background: In our day-to-day life, we are facing many dreadful diseases caused by many infectious pathogens. These pathogens invade the living organisms (host) and lethally damaging them. These dreadful pathogens were also be used as bioweapons. Among them, Clostridium perfringens is taken for the study. Clostridium perfringens is an anaerobic, rod shaped, gram positive bacteria capable of forming spores. It is prevalent in the environment and in the intestine of humans and other animals. It is the causative agent for a wide range of diseases including food borne diseases, gas gangrene and flesh eating disease called necrotizing fasciitis. C. perfringens is commonly found on raw meat and poultry that espouse to grow in conditions with very little or no oxygen, and under ideal conditions can multiply very rapidly. These conditions are occasionally lethal due to the substantial number of toxins such as alpha toxin, beta toxin, epsilon toxin and iota toxin produced by C. perfringens. It is significantly important to analyze the Drug targets of the pathogen in order to destroy them. Objective: The present work aims in identifying potential drug targets in C. perfringens through metabolic pathway analysis. Method: Primarily, the metabolic pathways of the host and pathogen are compared to identify unique pathways in the bacteria. Among the enzymes that catalyze unique metabolic pathways, the essential ones for the survival of the pathogen are identified. The druggability of the essential enzymes are predicted through identification of its sub cellular localization and other druggable parameters. Results: The comparative metabolic pathway analysis result shows that, among the 98 metabolic pathways of C.perfringens, 25 pathways were unique that they did not have a counterpart with Human. There were 113 enzymes involved in these unique pathways. The NCBI’s protein Blast search against human was done to identify the non-homologous proteins. There were 93 non-homologous proteins. Among the 93 non-homologous proteins, 47 proteins were found to be essential. Based on their sub-cellular localization, 32 proteins were identified as potential drug targets and 15 are probable vaccine candidates. Conclusion: The present work which started with 25 different pathways with more than a hundred different enzymes, resulted in the identification of 32 putative drug targets against C.perfringens infection. All these 32 identified targets did not have any human homolog and are highly essential for the survival of the organism. They were concluded as potential drug targets. Designing of compounds to inhibit these enzymes would be successful for treating the life threatening infections caused by this pathogen.

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