Dataset Information

Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue.

ABSTRACT: Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial brain resection was required to reach deep-seated lesions. Levels of proline oxidase/proline dehydrogenase (POX/PRODH), Δ¹-pyrroline-5-carboxylate reductases (PYCR1/2/3), prolidase (PEPD), and metalloproteinases (MMP-2, MMP-9) were assessed, along with the concentration of proline and proline-related metabolites. In comparison to normal brain tissue, POX/PRODH expression in GG4 was found to be suppressed, while PYCR1 expression and activity of PEPD, MMP-2, and -9 were upregulated. The GG4 proline concentration was 358% higher. Hence, rewiring of the proline metabolism in GG4 was confirmed for the first time, with a low-POX/PRODH/high-PYCR profile. High PEPD and MMPs activity is in keeping with GG4-increased collagen turnover and local aggressiveness. Further studies on the mechanisms of the interplay between altered proline metabolism and the GG4 microenvironment are warranted.

SUBMITTER: Sawicka MM

PROVIDER: S-EPMC10814259 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue.

Sawicka Magdalena M MM Sawicki Karol K Jadeszko Marek M Bielawska Katarzyna K Supruniuk Elżbieta E Reszeć Joanna J Prokop-Bielenia Izabela I Polityńska Barbara B Jadeszko Mateusz M Rybaczek Magdalena M Latoch Eryk E Gorbacz Krzysztof K Łysoń Tomasz T Miltyk Wojciech W

Cancers 20240121 2

Proline metabolism has been identified as a significant player in several neoplasms, but knowledge of its role in gliomas is limited despite it providing a promising line of pursuit. Data on proline metabolism in the brain are somewhat historical. This study aims to investigate alterations of proline metabolism in gliomas of WHO grade 4 (GG4) in the context of the brain. A total of 20 pairs of samples were studied, consisting of excised tumor and unaffected brain tissue, obtained when partial br ...[more]

PMID: 38275897

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Project description:The study was to investigate the effect of early-weaning stress and proline (Pro) and putrescine (Put) supplementations on serum biochemical parameters and amino acids (AA) metabolism in suckling and post-weaning pigs. Blood and small intestinal mucosa were harvested from suckling piglets at 1, 7, 14, and 21 d of age and piglets on d 1, 3, 5, and 7 after weaning at 14 d of age, as well as from piglets received oral administration of Pro and Put from 1 to 14 d old. In suckling piglets, the serum glucose, albumin and total cholesterol levels were increased (P < 0.05) with increasing age, whereas the serum globulin, urea nitrogen (BUN), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels were lowered (P < 0.05). The concentrations of most serum AA and the AA transporters related gene expressions were highest in 7-d-old piglets (P < 0.05), whereas the phosphorylation status of the mammalian target of the rapamycin (mTOR) signaling pathway in the small intestine increased in piglets from 1 to 21 d old (P < 0.05). Weaning at 14 d old increased (P < 0.05) the BUN and triglycerides levels in serum, as well as jejunal solute carrier family 7 member 6 (SLC7A6), ileal SLC36A1 and SLC1A1 mRNA abundances at d 1 or 3 post-weaning. Weaning also inhibited (P < 0.05) the phosphorylation levels of mTOR and its downstream ribosomal protein S6 kinase 1 (S6K1) and 4E-binding protein-1 (4EBP1) in the small intestine of weanling pigs. Oral administration of Put and Pro decreased (P < 0.05) serum ALP levels and increased (P < 0.05) intestinal SLC36A1 and SLC1A1 mRNA abundances and mTOR pathway phosphorylation levels in post-weaning pigs. Pro but not Put treatment enhanced (P < 0.05) serum Pro, arginine (Arg) and glutamine (Gln) concentrations of weaning-pigs. These findings indicated that early-weaning dramatically altered the biochemical blood metabolites, AA profile and intestinal mTOR pathway activity, and Pro and Put supplementations improved the AA metabolism and transportation as well as activated the intestinal mTOR pathway in weanling-pigs. Our study has an important implication for the broad application of Pro and Put in the weaning transition of piglets.

Dataset Information

Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue.

Publications

Proline Metabolism in WHO G4 Gliomas Is Altered as Compared to Unaffected Brain Tissue.

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