Cadmium Inhibition of the Sodium‐Glucose Transporter

Abstract

Cadmium (Cd2+) is a toxic metal found in the environment, a product of industrial pollution, and can enter the body through inhalation. Chronic exposure to Cd2+ causes kidney failure characterized by Fanconi‐like Syndrome, in which an array of sodium‐dependent nutrient transport is inhibited. Cd2+ causes a concentration‐dependent reduction in sodium‐glucose co‐transport that is correlated to the sodium‐glucose transporter (SGLT1) gene expression in kidney proximal tubule epithelial cells. SGLT1 is regulated by the zinc finger transcription factor, Sp1. In the presence of Cd2+, the zinc ion is displaced by a Cd2+ ion, resulting in the loss of transcriptional regulation of SGLT1. The structure of human SGLT1 is not known; as such the Shorewood SMART Team (Students Modeling A Research Topic) modeled a bacterial homolog of SGLT1 using 3D printing technology. The SGLT1 protein transmembrane helices (TM2E, TM3, TM7E, TM8, and TM11) and amino acids on these helices vital for Na+ dependent glucose co‐transport are conserved. SGLT1 undergoes a conformational change enabling Na+ dependent glucose transport across the apical membrane of proximal tubule of kidney. In order to understand the glucose transport in the face of Cd2+ and to understand the underlying molecular mechanism responsible for SGLT1 glucose transport, it is essential to know the protein structure of SGLT1. Supported by a grant from NIH‐SEPA and NIH‐CTSA