https://www.cell.com/cell/pdf/S0092-8674(00)80602-9.pdf

Insights into the Function of Rim Protein in Photoreceptors and Etiology of Stargardt's Disease from the Phenotype in abcr Knockout Mice

Textbook of histology

https://www.cell.com/cell/pdf/0092-8674(87)90700-8.pdf

Regulation of transmembrane signaling by receptor phosphorylation

Agonist-promoted desensitization of adenylate cyclase is intimately associated with phosphorylation of the beta-adrenergic receptor in mammalian, avian, and amphibian cells. However, the nature of the protein kinase(s) involved in receptor phosphorylation remains largely unknown. We report here the identification and partial purification of a protein kinase capable of phosphorylating the agonist-occupied form of the purified beta-adrenergic receptor. The enzyme is prepared from a supernatant fraction from high-speed centrifugation of lysed kin- cells, a mutant of S49 lymphoma cells that lacks a functional cAMP-dependent protein kinase. The beta-agonist isoproterenol induces a 5- to 10-fold increase in receptor phosphorylation by this kinase, which is blocked by the antagonist alprenolol. Fractionation of the kin- supernatant on molecular-sieve HPLC and DEAE-Sephacel results in a 50- to 100-fold purified beta-adrenergic receptor kinase preparation that is largely devoid of other protein kinase activities. The kinase activity is insensitive to cAMP, cGMP, cAMP-dependent kinase inhibitor, Ca2+-calmodulin, Ca2+-phospholipid, and phorbol esters and does not phosphorylate general kinase substrates such as casein and histones. Phosphate appears to be incorporated solely into serine residues. The existence of this novel cAMP-independent kinase, which preferentially phosphorylates the agonist-occupied form of the beta-adrenergic receptor, suggests a mechanism that may explain the homologous or agonist-specific form of adenylate cyclase desensitization. It also suggests a general mechanism for regulation of receptor function in which only the agonist-occupied or "active" form of the receptor is a substrate for enzymes inducing covalent modification.

https://www.pnas.org/content/pnas/83/9/2797.full.pdf

Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor

Cellular signaling and factors involved in Müller cell gliosis: neuroprotective and detrimental effects.

GTP binding protein: Properties and lack of activation by phosphorylated rhodopsin

1 – Structure of the Eye

Injection of acetaminophen (APAP) (350 mg/kg body weight) into C57BL/6 mice in which cytochrome P450 (CYP) 1A1/1A2 had been induced produced acute cataract and other ocular tissue damage. Treatment of APAP-injected mice with one of the major organosulfides in garlic oil, diallyl disulfide (DADS) (200 mg/kg body weight), prevented cataract development and prolonged survival time. N-acetyl L-cysteine (NAC) (500 mg/kg body weight), a prodrug that stimulates glutathione synthesis, also prolonged survival time but was effective only weakly to prevent cataract formation. A combination of DADS and NAC completely prevented cataractogenesis, and all of the treated animals survived APAP toxicity. Neither DADS nor NAC inhibited CYP 1A1/1A2 induction as determined by their effect on the induction of hepatic microsomal ethoxyresorufin O-dealkylase (ERD) activity. However, in the in vitro enzyme assay, DADS, but not NAC, was a potent inhibitor of ERD activity (IC50 = 3.5 mM). Treatment with DADS or NAC slowed but did not stop the decrease of hepatic glutathione (GSH) content. At 4 hours after APAP injection, hepatic GSH began to increase only when DADS and NAC were administered together. These results suggest that the protective effect of DADS is due to its inhibition of biotransformation of APAP to the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) by CYP 1A1/1A2 enzymes and that NAC provides protection by increasing cellular cysteine level and GSH synthesis, thus facilitating detoxification of NAPQI by glutathione conjugation. Assay of plasma glutamate-pyruvate transaminase activity, an indicator of liver necrosis, showed that treatment with DADS and NAC together effectively protected the liver. Therefore, the decrease of GSH as much as 30% of normal concentration, by itself, is not responsible for liver damage. The primary cause of hepatic necrosis is rapid accumulation of NAPQI.

Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and N-acetylcysteine

The localization of PGE2 receptor subtypes (EP1, EP2 and EP3) in nonuveal tissues of porcine eye was investigated by immunocytochemical methods with polyclonal antibodies directed against conserved peptide sequences in the carboxyl terminal region of the receptor subtypes. EP1 was found only in corneal epithelium, while EP2 immunoreactivity was associated with corneal epithelium and endothelium and lens epithelium. EP3 receptor subtype was localized to all ocular tissues examined (except lens fiber cells), i.e. corneal epithelium and endothelium, lens epithelium, retinal photoreceptor and pigmented epithelium, bipolar cell, horizontal cell, amacrine cell, ganglion cell and Muller cell.

Immunocytochemical Localization of Prostaglandin E2 Receptor Subtypes in Porcine Ocular Tissues. I. Uveal Tissues

The carbohydrate moieties of gamma-glutamyltranspeptidase (gamma-GTP) purified from bovine kidney were chemically released as oligosaccharides. The oligosaccharide mixture was fractionated into a neutral fraction and three groups of acidic fractions containing one, two, and three sialic acid residues. Both the neutral fractions and the neutral oligosaccharide mixture obtained from the pooled sample of all acidic fractions by sialidase treatment were separated into seven components by Bio-Gel P-4 column chromatography. Structural studies of these components by sequential exoglycosidase digestion in combination with methylation analysis indicated that the gamma-GTP contains at least twelve neutral sugar chains which are either the high mannose type, or the bi- and triantennary complex type, and thirteen acidic sugar chains of the bi-, tri-, and tetraantennary complex type. The characteristics feature of the sugar chains of the gamma-GTP is that most of the complex type sugar chains contain an N-acetylglucosamine residue at the C-4 position of the beta-mannosyl residue of their trimannosyl core, and their outer chain moieties are enriched in non-reducing terminal beta-N-acetylglucosamine residues.

Hitoshi Shichi

Papers

GTP binding protein: Properties and lack of activation by phosphorylated rhodopsin

1 – Structure of the Eye

Prevention of acetaminophen-induced cataract by a combination of diallyl disulfide and N-acetylcysteine

Immunocytochemical Localization of Prostaglandin E2 Receptor Subtypes in Porcine Ocular Tissues. I. Uveal Tissues

Carbohydrate Structures of Bovine Kidney γ-Glutamyltranspeptidase