PloS one, 2016-09, Vol.11 (9), p.e0162908-e0162908
2016
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- Autor(en) / Beteiligte
- Titel
- Inflammatory Adipokines Decrease Expression of Two High Molecular Weight Isoforms of Tropomyosin Similar to the Change in Type 2 Diabetic Patients
- Ist Teil von
- PloS one, 2016-09, Vol.11 (9), p.e0162908-e0162908
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Cardiovascular disease and cancer are increased in Type 2 diabetes. TPM1 and TPM4 genes encode proteins associated with cardiovascular and neoplastic disease. High (HMW) and low (LMW) molecular weight isoforms from TPM1 and TPM4 are altered in several cancer cells and the 3'UTR of TPM1 mRNA is tumour suppressive. Leukocytes influence cardiovascular and neoplastic disease by immunosurveillance for cancer and by chronic inflammation in Type 2 diabetes and cardiovascular disease. The aim was to determine changes in expression of isoforms from TPM1 and TPM4 genes in leukocytes from Type 2 diabetic patients and to use the leukocyte cell line THP1 to identify possible mediators of changes in the patients. Gene expression was determined by RT-qPCR. In diabetes, expression of HMW isoforms from TPM1 were markedly decreased (0.55 v 1.00; p = 0.019) but HMW isoforms from TPM4 were not significantly different (0.76 v 1.00; p = 0.205). Within individual variance in expression of HMW isoforms was very high. The change in expression in HMW isoforms from TPM1 and TPM4 was replicated in THP1 cells treated with 1 ng/ml TNFα (0.10 and 0.12 v 1.00 respectively) or 10 ng/ml IL-1α (0.17 and 0.14 v 1.00 respectively). Increased insulin or glucose concentrations had no substantial effects on TPM1 or TPM4 expression. Decreased TPM1 mRNA resulted in decreases in HMW protein levels. Expression of HMW isoforms from TPM1 is decreased in Type 2 diabetes. This is probably due to increased levels of inflammatory cytokines TNFα and IL-1α in Type 2 diabetes. Lower levels of TPM1 mRNA reduce tumour suppression and could contribute to increased cancer risk in Type 2 diabetes. Decreased HMW tropomyosin isoforms are associated with cancer. Decreased HMW isoforms give rise to cells that are more plastic, motile, invasive and prone to dedifferentiation resulting in leukocytes that are more invasive but less functionally effective.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0162908Titel-ID: cdi_plos_journals_1821788567
- Format
- –
- Schlagworte
- 3' Untranslated regions, Adipokines - pharmacology, Biology and Life Sciences, Blotting, Western, Cancer, Cancer prevention, Cardiovascular disease, Cardiovascular diseases, Cell Line, Tumor, Cytokines, Diabetes mellitus, Diabetes mellitus (non-insulin dependent), Diabetes Mellitus, Type 2 - genetics, Diabetes Mellitus, Type 2 - metabolism, Diabetics, Female, Gene expression, Gene Expression - drug effects, Genes, Genetic aspects, Glucose, Glucose - pharmacology, Health aspects, Health risks, Humans, Hypoglycemic Agents - pharmacology, Immunosurveillance, Inflammation, Inflammation Mediators - pharmacology, Insulin, Insulin - pharmacology, Insulin resistance, Interleukin-1alpha - pharmacology, Invasiveness, Isoforms, Kinases, Leukocytes, Leukocytes - drug effects, Leukocytes - metabolism, Male, Medicine and Health Sciences, Molecular chains, Molecular Weight, Muscle proteins, Ovarian cancer, Patients, Physical Sciences, Plastics, Protein Isoforms - chemistry, Protein Isoforms - genetics, Protein Isoforms - metabolism, Proteins, Reverse Transcriptase Polymerase Chain Reaction, RNA, RNA, Messenger - genetics, RNA, Messenger - metabolism, Tropomyosin, Tropomyosin - chemistry, Tropomyosin - genetics, Tropomyosin - metabolism, Tumor Necrosis Factor-alpha - pharmacology, Tumor necrosis factor-α, Tumors, Type 2 diabetes, White blood cells