Populations at risk for Mn toxicity include patients with iron deficiency or liver cirrhosis, recipients of Mn-supplemented total parenteral nutrition, and miners and welders who inhale Mn-rich fumes and particulates ( 2– 5). Mn excess can lead to neurological deficits and a disease known as manganism, with psychological and motor disturbances similar but not identical to those seen in idiopathic Parkinson’s disease ( 1, 2). IntroductionĪcquired from the diet, manganese (Mn) is an essential nutrient. Overall, these results indicated that Slc30a10 is essential for Mn excretion by hepatocytes and enterocytes and could be an effective target for pharmacological intervention to treat Mn toxicity. Finally, mice with Slc30a10 deficiency in liver and small intestines developed Mn excess that was less severe than that observed in mice with whole-body Slc30a10 deficiency, suggesting that additional sites of Slc30a10 expression contribute to Mn homeostasis.
Slc30a10 also localized to the apical membrane of enterocytes, but mice with Slc30a10 deficiency in small intestines developed minimal Mn excess despite impaired Mn export into the lumen of the small intestines. Slc30a10 localized to canalicular membranes of hepatocytes, but mice with liver Slc30a10 deficiency developed minimal Mn excess despite impaired biliary Mn excretion. To investigate the role of SLC30A10 in Mn homeostasis, we first generated whole-body Slc30a10–deficient mice, which developed severe Mn excess and impaired systemic and biliary Mn excretion. The first known disease of inherited Mn excess, identified in 2012, is caused by mutations in the metal exporter SLC30A10 and is characterized by Mn excess, dystonia, cirrhosis, and polycythemia. Toxicity classically results from inhalational exposures in individuals who work in industrial settings.
Manganese (Mn), an essential metal and nutrient, is toxic in excess.
0 kommentar(er)
