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Spermine-induced DNA methylation change in human macrophages

ABSTRACT: Polyamines, crucial molecules involved in cell proliferation and growth, play a pivotal role in cancer development and progression. Within the tumor microenvironment, macrophages, key components of the immune system, exhibit a complex relationship with polyamines. Evidence suggests that polyamines can modulate macrophage polarization, influencing their functional phenotypes. Here, we detected the gene DNA methylation changes in spermine-stimulated human macrophages isolated from PBMCs and TAMs.

ORGANISM(S): Paslahepevirus balayani Mycobacterium canetti Yersinia pestis Streptobacillus moniliformis Mycobacterium tuberculosis variant bovis Escherichia coli O157:H7 Francisella tularensis subsp. novicida Mycobacterium avium Bartonella henselae Rickettsia typhi Leptospira interrogans Mammarenavirus choriomeningitidis Toxoplasma gondii Orthohantavirus seoulense Francisella tularensis subsp. holarctica Yersinia enterocolitica Bartonella quintana Homo sapiens Campylobacter jejuni Mycobacterium avium subsp. paratuberculosis Francisella tularensis subsp. mediasiatica Orthohantavirus puumalaense Mycobacterium tuberculosis Salmonella enterica subsp. enterica serovar Typhimurium Francisella tularensis subsp. tularensis Mycobacterium tuberculosis variant microti Rickettsia prowazekii Staphylococcus aureus Yersinia pseudotuberculosis Cowpox virus

PROVIDER: GSE267014 | GEO | 2024/05/13

REPOSITORIES: GEO

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Spermine-induced gene expression change in human macrophages

Project description:Polyamines, crucial molecules involved in cell proliferation and growth, play a pivotal role in cancer development and progression. Within the tumor microenvironment, macrophages, key components of the immune system, exhibit a complex relationship with polyamines. Evidence suggests that polyamines can modulate macrophage polarization, influencing their functional phenotypes. Here, we detected the gene expression changes in spermine-stimulated human macrophages isolated from PBMCs.

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Project description:Spermine-induced DNA methylation change in human macrophages

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Physiological concentration changes of intracellular spermine activates DNA methyltransferase 3A and 3B and affects gene methylation

Project description:Polyamines are essential for various cell functions and are produced in most cells, as well as being taken up from extracellular sources. Polyamines, especially spermine, in blood cells increase when polyamines are supplied from the digestive tract. Altered polyamine metabolism has an impact on substrate concentrations and enzyme activities involved in gene methylation, and may affect gene expression. Therefore, we investigated the effect of decreased polyamine synthesis and extracellular spermine supply on substrate concentrations and enzyme activities involved in gene methylation and on changes of methylation in promoter regions using methylation arrays. In Jurkat cells and human mammary epithelial cells, changes in polyamine concentrations differed after polyamine synthesis inhibition. However, S-adenosylmethionine decarboxylase activity and the decarboxylated S-adenosylmethionine to S-adenosyl-L-methionine ratio were decreased by spermine addition in both cells. After inhibiting polyamine synthesis in Jurkat cells by D,L-alpha-difluoromethylornithine, the protein levels of DNA methyltransferase (DNMT) 1, 3A and 3B were not changed, but the activity of the three enzymes markedly decreased. The protein levels of these enzymes were not changed by addition of spermine; however, DNMT 3B was markedly activated and DNMT 3A was also activated. DNMT 1 was not activated. Effects on methylation of promoter regions included significant changes for tumor suppressor genes in response to altered polyamine metabolism. However, no significant changes in methylation status were found on genes of which methylation status and their related protein levels were affected by spermine. When considering these results, there are many genes for which polyamines have an impact on expression via methylation of promoter regions.

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