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Antioxidant molecular mechanism of adenosyl homocysteinase from cyanobacteria and its wound healing process in fibroblast cells.

ABSTRACT: An antioxidant molecule namely, adenosyl homocysteinase (AHc) was identified from the earlier constructed transcriptome database of Spirulina, where it was cultured in a sulphur deprived condition. From the AHc protein, a small peptide NL13 was identified using bioinformatics tools and was predicted to have antioxidant property. Further, the peptide was synthesised and its antioxidant mechanism was addressed at molecular level. NL13 was subjected to various antioxidant assays including DPPH assay, HARS assay, SARS Assay, NO assay and ABTS assay, where NL13 exhibited significant (P?

SUBMITTER: Sarkar P

PROVIDER: S-EPMC7223595 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Antioxidant molecular mechanism of adenosyl homocysteinase from cyanobacteria and its wound healing process in fibroblast cells.

Sarkar Purabi P Stefi Raju V RV Pasupuleti Mukesh M Paray Bilal Ahmad BA Al-Sadoon Mohammad K MK Arockiaraj Jesu J

Molecular biology reports 20200127 3

An antioxidant molecule namely, adenosyl homocysteinase (AHc) was identified from the earlier constructed transcriptome database of Spirulina, where it was cultured in a sulphur deprived condition. From the AHc protein, a small peptide NL13 was identified using bioinformatics tools and was predicted to have antioxidant property. Further, the peptide was synthesised and its antioxidant mechanism was addressed at molecular level. NL13 was subjected to various antioxidant assays including DPPH assa ...[more]

PMID: 31989428

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Project description:Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play major roles in skin wound healing such as in wound contraction and release of growth factors which are of importance in angiogenesis and tissue remodeling. Abnormal fibroblast phenotypes have been identified in patients with chronic wounds. In this work, we analyzed scRNA-seq datasets of normal and wounded skin from mice at day 4 post-wound to investigate fibroblast heterogeneity during the proliferative phase of wound healing. Compositional analysis revealed a specific subset of fibroblast (cluster 3) that primarily increased in wounded skin (14%) compared to normal skin (3.9%). This subset was characterized by a gene signature marked by the plasma membrane proteins Sfrp2 + Sfrp4 + Sfrp1 + and the transcription factors Ebf1 + Prrx1 + Maged1 + . Differential gene expression and enrichment analysis identified epithelial to mesenchymal transition (EMT) and angiogenesis to be upregulated in the emerging subset of fibroblasts of the wounded skin. Using two other datasets for murine wounded skin confirmed the increase in cluster 3-like fibroblasts at days 2, 7 and 14 post-wounding with a peak at day 7. By performing a similarity check between the differential gene expression profile between wounded and normal skin for this emerging fibroblast subset with drug signature from the ConnectivityMap database, we identified drugs capable of mimicking the observed gene expression change in fibroblasts during wound healing. TTNPB, verteprofin and nicotinic acid were identified as candidate drugs capable of inducing fibroblast gene expression profile necessary for wound healing. On the other hand, methocarbamol, ifosfamide and penbutolol were recognized to antagonize the identified fibroblast differential expression profile during wound healing which might cause delay in wound healing. Taken together, analysis of murine transcriptomic skin wound healing datasets suggested a subset of fibroblasts capable of inducing EMT and further inferred drugs that might be tested as potential candidates to induce wound closure.

Project description:Background: The Balaruc-les-Bains' thermal mud was found to be colonized predominantly by microorganisms, with cyanobacteria constituting the primary organism in the microbial biofilm observed on the mud surface. The success of cyanobacteria in colonizing this specific ecological niche can be explained in part by their taxa-specific adaptation capacities, and also the diversity of bioactive natural products that they synthesize. This array of components has physiological and ecological properties that may be exploited for various applications. Methods: Nine cyanobacterial strains were isolated from Balaruc thermal mud and maintained in the Paris Museum Collection (PMC). Full genome sequencing was performed coupled with targeted and untargeted metabolomic analyses (HPLC-DAD and LC-MS/MS). Bioassays were performed to determine antioxidant, anti-inflammatory, and wound-healing properties. Results: Biosynthetic pathways for phycobiliproteins, scytonemin, and carotenoid pigments and 124 metabolite biosynthetic gene clusters (BGCs) were characterized. Several compounds with known antioxidant or anti-inflammatory properties, such as carotenoids, phycobilins, mycosporine-like amino acids, and aeruginosins, and other bioactive metabolites like microginins, microviridins, and anabaenolysins were identified. Secretion of the proinflammatory cytokines TNF-?, IL-1?, IL-6, and IL-8 appeared to be inhibited by crude extracts of Planktothricoides raciborskii PMC 877.14, Nostoc sp. PMC 881.14, and Pseudo-chroococcus couteii PMC 885.14. The extract of the Aliinostoc sp. PMC 882.14 strain was able to slightly enhance migration of HaCat cells that may be helpful in wound healing. Several antioxidant compounds were detected, but no significant effects on nitric oxide secretion were observed. There was no cytotoxicity on the three cell types tested, indicating that cyanobacterial extracts may have anti-inflammatory therapeutic potential without harming body cells. These data open up promising uses for these extracts and their respective molecules in drugs or thermal therapies.

Dataset Information

Antioxidant molecular mechanism of adenosyl homocysteinase from cyanobacteria and its wound healing process in fibroblast cells.

Publications

Antioxidant molecular mechanism of adenosyl homocysteinase from cyanobacteria and its wound healing process in fibroblast cells.

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