Transport pathways for cadmium in the intestine and kidney proximal tubule: focus on the interaction with essential metals.
Cadmium (Cd) is a toxic metal with a propensity to accumulate in the proximal tubules cells (PTC) of the kidney where it can lead to tubular dysfunction and eventually renal failure. Although Cd(2+)-induced nephrotoxicity has been well described there is still uncertainty about how this metal gains entry into these cells to induce toxicity. As a non-essential metal, specific transport proteins for Cd are unlikely to exist. Rather transport proteins/channels used by essential metals (iron, zinc, calcium) are thought to be responsible. When these dietary essential metals are in short supply and deficiencies develop, Cd absorption and toxicity are enhanced. This is primarily due to increased expression of essential metal transport proteins such as divalent metal transporter 1 (DMT1) which can transport Cd in the intestine and enhance toxicity in the kidney. The zinc/bicarbonate sympoters ZIP8 and 14 are expressed at the apical membrane of enterocytes and PTC, and can transport Cd into cells. TRPV5 and 6 are major transporters for calcium in intestine and kidney and may be involved in Cd transport in these locations. Cd in the circulation is bound to proteins such as metallothioneins (MT) which are readily filtered. Two multiligand receptors, megalin and cubulin, reabsorb filtered proteins including albumin and MT by the process of receptor-mediated endocytosis. This review summarises the transport pathways for Cd in the intestine and kidney proximal tubule focusing in particular at how Cd uses essential metal transport processes to gain entry to the circulation and the kidney.
Vesey
David A
DA
Department of Nephrology, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland 4102, Australia. David_Vesey@health.qld.gov.au
D002104:Cadmium / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D015386:Hazardous Substances / Q000493:pharmacokinetics* / Q000633:toxicity; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
D015386:Hazardous Substances; D002104:Cadmium; D008668:Metallothionein; D007501:Iron; D015032:Zinc; D002118:Calcium