title: Effect of magnesium deficiency on intracellular ATP levels in human lens epithelial cells.
abstract: Cataractous lenses have an altered distribution of the intracellular ionic environment, and the lens ionic imbalance with increased levels of calcium (Ca2+) and sodium (Na+), coupled with decreased levels of magnesium (Mg2+) and potassium (K+), is related to cataract development in human senile cataracts. We previously found that the decrease of ATP in lenses caused lens ionic imbalance, and probably decrease in ATPase function. In this study, we investigated the effect of Mg2+ deficiency on cataract progression using human lens epithelial (HLE) cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA in HLE cells were significantly greater in Mg2+-deficient medium (Mg2+ 0.021 mM) than in normal Mg2+ medium (Mg2+ 0.77 mM). The NO release from the HLE cells cultured with Mg2+-deficient medium also increased. On the other hand, the ATP levels in HLE cells 24 h after incubation with Mg2+-deficient medium were lower than that with normal Mg2+ medium. The Ca2+- and Na+/K+-ATPase activities in HLE cells until 24 h incubation with normal Mg2+ or Mg2+-deficient medium did not change. Both diethyldithiocarbamate 10 microM and aminoguanidine 250 microM attenuated the increase of NO release, and caused an increase in ATP levels in HLE cells 24 h after incubation with Mg2+-deficient medium. These results suggest that Mg2+ deficiency enhances NO production via iNOS in the lens. It is possible that the excessive production of NO cause the decrease of ATP levels. These results show that Mg2+ deficiency in the lens may cause an acceleration of the progression of lens opacification.
authors.affiliation: Kinki University School of Pharmacy, Osaka, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nagai
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuhata
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002386:Cataract / Q000209:etiology; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D018450:Disease Progression; D004050:Ditiocarb / Q000494:pharmacology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008274:Magnesium / Q000378:metabolism*; D008275:Magnesium Deficiency / Q000150:complications / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013997:Time Factors
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D004050:Ditiocarb; D052247:Nitric Oxide Synthase Type II; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium; C004479:pimagedine