Increased activity of the sodium transporter, sodium-lithium countertransport (SLC), is reported in hypertensive white patients with evidence of cardiac and renal injury. The purpose of this study was to determine whether increased SLC activity detects risk for nephropathy or vascular disease in nondiabetic, young adult African-Americans. We examined 85 African-Americans aged 25 to 33 years with measurement of blood pressure, an oral glucose tolerance test to measure insulin response to glucose challenge, and an insulin clamp for insulin sensitivity (M). Fasting plasma lipids were measured, and the Vmax and Km for Na+ were assayed on red blood cells. Urinary albumin excretion (UAE) was measured on timed collections. There was a statistically significant correlation of the Vmax for SLC with M (r = -0.26, P = 0.02) and with UAE (r = 0.25, P = 0.02). The Km for Na+ to activate SLC was also elevated in the subgroup of subjects with elevated Vmax of SLC. There was no significant correlation of SLC with blood pressure in bivariate analysis. Step-wise multiple linear regression analysis of all variables on the Vmax SLC demonstrated that plasma triglyceride, UAE, body mass index, systolic blood pressure, M, and fasting insulin were step-wise selected into the linear regression model (F-ratio = 3.2, df = 77, R = 0.46, P < 0.009). In this young adult African-American population, elevated SLC activity is detected in association with metabolic and lipid alterations typical of insulin resistance. Elevated SLC activity is also associated with higher rates of UAE, suggesting possible evidence of early renal injury.
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Nat Commun
January 2025
Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Guwahati, India.
This study is focused on the design, synthesis, and evaluation of some sulfonamide derivatives for their inhibitory effects on human carbonic anhydrase (hCA) enzymes I, II, IX, and XII as well as for their antioxidant activity. The purity of the synthesized molecules was confirmed by the HPLC purity analysis and was found in the range of 93%-100%. The inhibition constant (K) against hCA I ranged from 0.
View Article and Find Full Text PDFBackground And Aim: The high rate of tumor growth results in an increased need for amino acids. As solute carriers (SLC) transporters are capable of transporting different amino acids, cancer may develop as a result of these transporters' over-expression due to their complex formation with other biological molecules. Therefore, this review investigated the role of SLC transporters in the progression of cancer.
View Article and Find Full Text PDFAnticancer Res
December 2024
Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, P.R. China;
Background/aim: Solute carrier (SLC) family 15 member 2 (SLC15A2) is an integral member of the SLC family that plays a pivotal role in numerous biological processes, including the regulation of cellular signaling pathways. However, its role in prostate cancer (PCa) remains inadequately elucidated. This study aims to investigate the prognostic significance of SLC15A2 in PCa.
View Article and Find Full Text PDFBiosci Rep
December 2024
University of Lincoln College of Science, Lincoln, United Kingdom.
Cellular Ca2+ homeostasis is critical for normal cell physiology and is regulated by several mechanisms. Two major players in intracellular Ca2+ homeostasis in multiple tissues belong to SLC8 (Na+/Ca2+ exchangers (NCXs); NCX1-3) and SLC24 (K+ dependent Na+/Ca2+ exchangers (NCKXs); NCKX1-5) families. It has been established that NCXs and NCKX4 are palmitoylated, and that palmitoylation promotes NCX1 inactivation.
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