title: DNA-synthesis regulation and correlation with inositol trisphosphate levels in cultured bovine retinal capillary pericytes.
abstract: Inositol phosphate (IP), inositol bisphosphate (IP2) and inositol trisphosphate (IP3) in cultured bovine retinal capillary pericytes (BRCP) were quantitated by an ion-pair reverse-phase HPLC. BRCP were grown in media with standard (5 mM) or high (30 mM) glucose, and were either labeled with myo-[2-3H]inositol (20 microCi ml-1) for 60 hr or with dual isotopes (20 microCi ml-1 myo-[2-3H]inositol and 2 microCi ml-1 [14C]glycerol) for 8 hr. In parallel, BRCP in different glucose-media were incubated with 1 microCi ml-1 [3H]thymidine for 4 hr. High glucose significantly suppressed the accumulation of [3H]label in IP, IP2 and IP3, and specifically reduced the incorporation of [14C]glycerol into inositol phospholipids, but not that of neutral lipids and other types of phospholipids. The reduced IP3 level correlated with the decrease in the incorporation of [3H]thymidine into DNA. Both the reduced IP3 formation and DNA synthesis which were induced by high glucose were significantly reversed by adding either myo-inositol or AL1576, an aldose reductase inhibitor (ARI). However, the addition of neither myo-inositol nor ARI stimulated IP3 formation and/or DNA synthesis when BRCP were grown in the standard medium (5 mM glucose). These findings indicate that myo-inositol metabolism and the polyol pathway affect inositol phospholipid-mediated pericyte division in vitro only under the high-glucose condition. These data are compatible with the hypothesis that altered inositol phospholipid metabolism accounts for the loss of pericytes in diabetic retinopathy.
authors: Department of Ophthalmology, Peking Union Medical College Hospital, Beijing, China.
authors: W Y
authors: WY
authors: Li
authors: L
authors: L
authors: Tang
authors: Q
authors: Q
authors: Zhou
authors: M
authors: M
authors: Qin
authors: T S
authors: TS
authors: Hu
mesh_terms: D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D007292:Inosine Nucleotides / Q000378:metabolism*; D007293:Inosine Triphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D012171:Retinal Vessels / Q000166:cytology / Q000378:metabolism*
chemical_list: D007292:Inosine Nucleotides; D007295:Inositol Phosphates; D007293:Inosine Triphosphate; D004247:DNA