Inflammatory Adipokines Decrease Expression of Two High Molecular Weight Isoforms of Tropomyosin Similar to the Change in Type 2 Diabetic Patients.

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.

Functional structure of the promoter regions for the predominant low molecular weight isoforms of tropomyosin in human kidney cells.

High and low molecular weight (LMW) tropomyosin isoforms, by regulation of actin filaments, have a major role in the regulation of cell behaviour. They affect malignant transformation, motility, differentiation, metastasis and cell membrane protein presentation. Expression of LMW isoforms from the TPM1 and TPM3 genes have an important role in these effects but the regulation of their expression is unknown.

Polymorphisms in the tropomyosin TPM1 short isoform promoter alter gene expression and are associated with increased risk of metabolic syndrome.

Background: Inflammation contributes to the development of atherosclerotic lesions in the metabolic syndrome. Tropomyosin isoform expression is altered in this disease and has a role in inflammatory cell plasticity, motility, and insulin sensitivity. We determined the frequency of haplotype carriage of three single-nucleotide polymorphisms (SNPs) in the short isoform promoter of the TPM1 gene in 300 normal controls and 500 metabolic syndrome patients.

Sodium-lithium countertransport and the Gly460-->Trp alpha-adducin polymorphism in essential hypertension.

A polymorphism of the alpha-subunit of adducin, Gly460-->Trp, may affect membrane ion transport and be associated with human EH (essential hypertension). The alpha-adducin Gly460-->Trp polymorphism was determined in 242 NC (normal controls) and 73 patients with EH and was related to the membrane ion transport marker in EH, erythrocyte Na/LiCT (sodium-lithium countertransport), in a subgroup of these subjects. The Km for external sodium was lower in patients with EH than NC.

Altered tropomyosin expression in essential hypertension.

Abnormal erythrocyte sodium-lithium countertransport is common in a subgroup of patients with essential hypertension and a strong family history of hypertension and cardiovascular disease. We have previously shown that the abnormality in sodium-lithium countertransport is associated with tropomyosin, a cytoskeletal protein required to stabilize actin filament formation. Leukocyte trafficking events, which depend on cytoskeletal reorganization, are also altered in patients with essential hypertension with abnormal sodium-lithium countertransport.

Abnormalities in primary granule exocytosis in neutrophils from Type I diabetic patients with nephropathy.

Microalbuminuria in Type I diabetes involves a cell membrane abnormality and is associated with a large increase in cardiovascular risk. The hypothesis that the membrane abnormality alters granule exocytosis in neutrophils, which could contribute to the increased incidence of cardiovascular disease, was investigated. PMA-stimulated expression of CD11b and CD69 on neutrophils from normal controls (NC), long-term uncomplicated Type I diabetic control patients (DC) and diabetic nephropathy patients (DN) was determined by fluorescence activated cell scanning.