Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Attenuation of both the active transport of myo-inositol and Na(+)-K(+)-ATPase pumping activity has been implicated in the onset of sugar cataract and other diabetic complications in cell culture and animal models of the disease. Cultured bovine lens epithelial cells (BLECs) maintained in galactose-free Eagle's minimal essential medium (MEM) or 40 mM galactose with and without sorbinil for up to 5 days were examined to determine the temporal effects of hypergalactosemia on Na(+)-K(+)-ATPase and myo-inositol uptake. The Na(+)-K(+)-ATPase pumping activity after 5 days of continuous exposure to galactose did not change, as demonstrated by 86Rb uptake. The uptake of myo-[3H]inositol was lowered after 20 h of incubation in galactose and remained significantly below that of the control throughout the 5-day exposure period. The coadministration of sorbinil to the galactose medium normalized the myo-[3H]inositol uptake. No significant difference in the rates of passive efflux of myo-[3H]inositol or 86Rb from preloaded galactose-treated and control cultures was observed. Culture-media reversal studies were also carried out to determine whether the galactose-induced dysfunction in myo-inositol uptake could be corrected. BLECs were incubated in galactose for 5 days, then changed to galactose-free physiological medium with and without sorbinil for a 1-day recovery period. myo-Inositol uptake was reduced to 34% of control after 6 days of continuous exposure to galactose. Within 24 h of media reversal, myo-inositol uptake returned to or exceeded control values in BLECs switched to either MEM or MEM with sorbinil.2+ reversible and occurred independently of changes in Na(+)-K(+)-ATPase pumping activity in cultured lens epithelium, indicating that the two parameters are not strictly associated and that the deficit in myo-inositol uptake occurs rapidly during hypergalactosemia.
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PMID:Uncoupling of attenuated myo-[3H]inositol uptake and dysfunction in Na(+)-K(+)-ATPase pumping activity in hypergalactosemic cultured bovine lens epithelial cells. 164 82

The extent of glycation of human eye lens proteins with glucose in presence of added inositol was examined in vitro using [U14C] glucose. Lens homogenate was reacted with varying concentrations of glucose and glucose + inositol. At the end of the reaction, the proteins were precipitated with TCA, centrifuged, dissolved in NaOH and the radioactivity was measured. Inositol decreased the glycation by 57-67%. Pure inositol and glucose suitably labelled with 3H or 14C when reacted and followed by paper chromatography and HPLC showed that glucosyl inositol was present along with unreacted free glucose. Preliminary studies made of the UV spectra of pure inositol (i) when reacted with H2O2 showed that inositol removed H2O2 from the reaction mixture (ii) when reacted with arachidonic acid showed that they formed a conjugate. The observations indicate that the antioxidant property of inositol could be the result of its' quenching action on reactive oxygen, intermediates and conjugate-formation with compounds like arachidonic acid and the antiglycating property due to scavenging of glucose. The antioxidant and the antiglycating properties of inositol may be beneficial in delaying or averting cataract.
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PMID:Two new functions of inositol in the eye lens: antioxidation and antiglycation and possible mechanisms. 1054 73

Alterations of intracellular levels of myo-inositol (MI) have the potential to impact such cellular processes as signaling pathways and osmotic balance. Depletion of MI has been implicated in the etiology of diabetic complications; however, the mechanistic details remain sketchy. myo-Inositol oxygenase (MIOX-EC 1.13.99.1) catalyzes the first committed step of the only pathway of MI catabolism. In the present study, extra-renal tissues and cell types, including those affected by diabetic complications, were examined for MIOX expression. Western blotting results indicated that kidney is the only major organ where MIOX protein is expressed at detectable levels. Immunohistochemical examination of the kidney revealed that the proximal tubular epithelial cells are the only site of MIOX expression in the kidney. Reverse-transcription-polymerase chain reaction (RT-PCR) and Western immunoblot analyses, however, revealed that the cell lines ARPE-19 and HLE-B3, representing human retinal pigmented epithelium and lens epithelium, respectively, also express MIOX. In addition, quantitative real-time RT-PCR analysis of all major tissues in the mouse showed that the sciatic nerve contained MIOX transcript, which was found to be significantly higher than that observed in other non-renal organs. These results indicate that MIOX is found at lower levels in extra-renal tissues where diabetic complications, including nephropathy, neuropathy, retinopathy, and cataract, are frequently observed.
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PMID:Expression of myo-inositol oxygenase in tissues susceptible to diabetic complications. 1633 55

INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is comprised of a N-terminal catalytic domain which hydrolyses both PtdIns(4,5)P2 and PtdIns(3,4,5)P3, followed by a SKICH domain at the C-terminus which is responsible for protein-protein interactions and subcellular localization of INPP5K. Strikingly, INPP5K is mostly concentrated in the endoplasmic reticulum, although it is also detected at the plasma membrane, in the cytosol and the nucleus. Recently, mutations in INPP5K have been detected in patients with a rare form of autosomal recessive congenital muscular dystrophy with cataract, short stature and intellectual disability. INPP5K functions extend from control of insulin signaling, endoplasmic reticulum stress response and structural integrity, myoblast differentiation, cytoskeleton organization, cell adhesion and migration, renal osmoregulation, to cancer. The goal of this review is thus to summarize and comment recent and less recent data in the literature on INPP5K, in particular on the structure, expression, intracellular localization, interactions and functions of this specific member of the 5-phosphatases family.
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PMID:The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions. 3306 52