Welders in this study were selected from a vehicle manufacturer; control subjects were from a nearby food factory. Airborne manganese levels in the breathing zones of welders and controls were 1.45 ± SD1.08 mg/m 3 and 0.11 ± 0.07 μg/m 3 , respectively. Serum levels of manganese and iron in welders were 4.3-fold and 1.9-fold, respectively, higher than those of controls. Blood lead concentrations in welders increased 2.5-fold, whereas serum zinc levels decreased 1.2-fold, in comparison with controls. Linear regression revealed the lack of associations between blood levels of five metals and welder's age. Furthermore, welders had erythrocytic superoxide dismutase activity and serum malondialdehyde levels 24% less and 78% higher, respectively, than those of controls. These findings suggest that occupational exposure to welding fumes among welders disturbs the homeostasis of trace elements in systemic circulation and induces oxidative stress.The welding fume generated during the welding process possesses at least 13 metals, including manganese (Mn), beryllium (Be), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), iron (Fe), lead (Pb), mercury (Hg), molybdenum (Mo), nickel (Ni), zinc (Zn), antimony (Sb), and vanadium (V). 1 Welders are known to be at risk, particularly for chronic exposure to airborne manganese, which is one of the major coating materials in welding products (eg, bars and wires). [2][3][4][5][6] A recent study even suggests that exposure to manganese during welding may be a risk factor for the etiology of Parkinson's disease among the career welders. 7 Although limited studies have documented airborne manganese levels during welding, the question as to how low-level, long-term exposure to manganese or welding fume may affect blood levels of trace metals is unanswered. However, altered systemic homeostasis of iron and manganese is known to be associated with neurodegenerative disorders. 8 Manganese-induced neurological lesions are reportedly located in the globus pallidus and striatum of the basal ganglia. The pallidus and striatum display a marked decrease in myelinated nerve fibers, accompanied by depletion of striatal dopamine. [11][12][13][14] The mechanism whereby manganese induces neurodegenerative damage remains elusive. Nonetheless, several recent reports have suggested that manganese neurotoxicity may be associated with its interaction with other essential trace elements, including iron, 10,13,15,16 zinc, 17 copper, 17 and aluminum. 13,15,18 Particularly regarding manganese-induced neurotoxicity, studies have shown that chronic exposure to manganese appears to be associated with altered iron concentrations in blood as well as in the cerebrospinal fluid, presumably the result of Mn-Fe interaction at certain [Fe-S]-containing proteins, which regulate the homeostasis of iron. 10,16,[19][20][21] The excess accumulation of iron in neurons may consequently produce cellular oxidative stress, leading to neuronal damage.Superoxide dismutase (SOD), a cytoplasmic enzyme, catalyzes the react...

Divalent metal transporter 1 (DMT1), whose mRNA possesses a stem-loop structure in 3′-untranslated region, has been identified in most organs and responsible for transport of various divalent metal ions. Previous work from this laboratory has shown that manganese (Mn) exposure alters the function of iron regulatory protein (IRP) and increases iron (Fe) concentrations in the cerebrospinal fluid (CSF). This study was designed to test the hypothesis that Mn treatment, by acting on protein-mRNA binding between IRP and DMT1 mRNA, altered the expression of DMT1 in an immortalized choroidal epithelial Z310 cell line which was derived from rat choroid plexus epithelia, leading to a compartmental shift of Fe from the blood to the CSF. Immunocytochemistry confirmed the presence of DMT1 in Z310 cell. Following in vitro exposure to Mn at 100 μM for 24 and 48 h, the expression of DMT1 mRNA in Z310 cells was significantly increased by 45.4% (P < 0.05) and 78.1% (P < 0.01), respectively, as compared to controls. Accordingly, Western blot analysis revealed a significant increase of DMT1 protein concentrations at 48 h after Mn exposure (100 μM). Electrophoretic mobility shift assay (EMSA) showed that Mn exposure increased binding of IRP to DMT1 mRNA in cultured choroidal Z310 cells. Moreover, real-time RT-PCR revealed no changes in DMT1 heterogeneous nuclear RNA (hnRNA) levels following Mn exposure. These data suggest that Mn appears to stabilize the binding of IRP to DMT1 mRNA, thereby increasing the expression of DMT1. The facilitated transport of Fe by DMT1 at the blood-CSF barrier may partly contribute to Mn-induced neurodegenerative Parkinsonism.