Alpha lipoic acid changes iron uptake and storage in lens epithelial cells.
Alpha lipoic acid (LA) is a cofactor in mitochondrial dehydrogenase complexes. Previous studies have shown that when administered exogenously LA has antioxidant properties, which include free radical scavenging, metal chelation and regeneration of other antioxidants. The cells convert LA into dihydroplipoic acid (DHLA), which in the presence of iron can act as a prooxidant. In vitro DHLA reduces Fe(+3) to Fe(+2) and removes iron from ferritin, increasing the risk of Fe catalyzed free radical formation. In the present study we examined the in vivo effects of lipoic acid treatment on Fe metabolism in cultured lens epithelial cells, and found that LA decreases Fe uptake from transferrin, increases Fe deposition into ferritin and increases the concentration of this protein. When administered together with ascorbic acid, lipoic acid changes the characteristic heavy to light chain ratio of ferritin makeup. The decreased Fe uptake and increased storage diminishes the size of the cytosolic highly reactive Fe pool (LIP). These changes are associated with increased cell resistance to H(2)O(2) challenge. Therefore, LA may reduce the risk of Fe induced oxidative damage and also might be useful as a treatment of Fe overload.
Goralska
Malgorzata
M
Department of Molecular Biomedical Sciences, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Dackor
Ryan
R
Holley
Benjamin
B
McGahan
M Christine
MC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005293:Ferritins / Q000096:biosynthesis / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007501:Iron / Q000493:pharmacokinetics*; D007903:Lens Capsule, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D008063:Thioctic Acid; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron; D001205:Ascorbic Acid