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Insight into the haem d1 biosynthesis pathway in heliobacteria through bioinformatics analysis.

ABSTRACT: Haem d(1) is a unique tetrapyrrole molecule that serves as a prosthetic group of cytochrome cd(1), which reduces nitrite to nitric oxide during the process of denitrification. Very little information is available regarding the biosynthesis of haem d(1). The extreme difficulty in studying the haem d(1) biosynthetic pathway can be partly attributed to the lack of a theoretical basis for experimental investigation. We report here a gene cluster encoding enzymes involved in the biosynthesis of haem d(1) in two heliobacterial species, Heliobacillus mobilis and Heliophilum fasciatum. The gene organization of the cluster is conserved between the two species, and contains a complete set of genes that lead to the biosynthesis of uroporphyrinogen III and genes thought to be involved in the late steps of haem d(1) biosynthesis. Detailed bioinformatics analysis of some of the proteins encoded in the gene cluster revealed important clues to the precise biochemical roles of the proteins in the biosynthesis of haem d(1), as well as the membrane transport and insertion of haem d(1) into an apocytochrome during the maturation of cytochrome cd(1).

SUBMITTER: Xiong J

PROVIDER: S-EPMC2774728 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Insight into the haem d1 biosynthesis pathway in heliobacteria through bioinformatics analysis.

Xiong Jin J Bauer Carl E CE Pancholy Anjly A

Microbiology (Reading, England) 20071001 Pt 10

Haem d(1) is a unique tetrapyrrole molecule that serves as a prosthetic group of cytochrome cd(1), which reduces nitrite to nitric oxide during the process of denitrification. Very little information is available regarding the biosynthesis of haem d(1). The extreme difficulty in studying the haem d(1) biosynthetic pathway can be partly attributed to the lack of a theoretical basis for experimental investigation. We report here a gene cluster encoding enzymes involved in the biosynthesis of haem ...[more]

PMID: 17906152

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Project description:IntroductionHepatocellular carcinoma (HCC) is an aggressive malignancy, and CCL18, a marker of M2 macrophage activation, is often associated with tumor immune suppression. However, the role of CCL18 and its signaling pathway in HCC is still limited. Our study focuses on investigating the prognostic impact of CCL18 and its signaling pathway in HCC patients and biological functions in vitro.MethodsHCC-related RNA-seq data were obtained from TCGA, ICGC, and GEO. The 6 hub genes with the highest correlation to prognosis were identified using univariate Cox and LASSO regression analysis. Multivariate Cox regression analysis was performed to assess their independent prognostic potential and a nomogram was constructed. In vitro experiments, including CCK8, EdU, RT-qPCR, western blot, and transwell assays, were conducted to investigate the biological effects of exogenous CCL18 and 6 hub genes. A core network of highly expressed proteins in the high-risk group of tumors was constructed. Immune cell infiltration was evaluated using the ESTIMATE and CIBERSORT packages. Finally, potential treatments were explored using the OncoPredict package and CAMP database.ResultsWe identified 6 survival-related genes (BMI1, CCR3, CDC25C, CFL1, LDHA, RAC1) within the CCL18 signaling pathway in HCC patients. A nomogram was constructed using the TCGA_LIHC cohort to predict patient survival probability. Exogenous CCL18, as well as overexpression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1, can promote proliferation, migration, invasion, stemness, and increased expression of PD-L1 protein in LM3 and MHCC-97H cell lines. In the high-risk group of patients from the TCGA_LIHC cohort, immune suppression was observed, with a strong correlation to 21 immune-related genes and suppressive immune cells.ConclusionExogenous CCL18 promotes LM3 and MHCC-97H cells proliferation, migration, invasion, stemness, and immune evasion. The high expression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1 can serve as a biomarkers for immune evasion in HCC.

Project description:Tendon injury is one of the most serious orthopedic diseases often leading to disability of patients. Major shortages of tendon healing are due to its multiple comorbidities, uncertainty of therapeutic efficacy and insufficient of angiogenesis. With a deeper understanding of angiogenic mechanism of tendon healing, we investigated an innovative microneedle patch loaded with platelet derived growth factor (PDGF) to achieve a constant systemic administration of PDGF to enhance topical tendon healing. Rat achilles tendon injury model was performed as in vivo animal models. Histological staining showed an enhancement of tendon healing quality, especially angiogenesis. Biomechanical studies demonstrated an increase of tendon stiffness, maximum load and maximum stress with treatment of PDGF-loaded microneedles. Furthermore, MAPK/p38/Cyclin D1 pathway and angiogenesis were found to play an important role in tendon healing process by using a biological high throughput RNA-sequence method and bioinformatic analysis. The high throughput RNA-seq tendon healing results were confirmed by histochemical staining and western blot. These results suggest the novel therapeutic potential of PDGF-loaded microneedle patch in tendon surgery. Graphical abstract PDGF-loaded PVA based microneedle was fabricated by Teflon mold method. In vivo studies showed an enhancement of tendon healing quality through angiogenesis in rat achilles tendon injury model. Followed up experiments including high-throughput RNA sequence further revealed role of MAPK/p38 pathways in PDGF tendon healing process. After combination of PDGF and PDGFR, MAPK/p38 signaling pathway was activated. Phosphorylation of p38 was entered into nucleus and combined with transcriptional factors. Two predicted promoters of Cyclin D, CREB and AP-1, downstream molecules of p38, were then transactivation and the expression of Cyclin D was upregulated. With the upregulation of Cyclin D, cell proliferation was enhanced leading to angiogenesis and tendon healing enhancement.Image 1

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Insight into the haem d1 biosynthesis pathway in heliobacteria through bioinformatics analysis.

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Insight into the haem d1 biosynthesis pathway in heliobacteria through bioinformatics analysis.

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