Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 23 kDa protein was localized by immunocytochemistry to photoreceptor cells of the mouse retina, and bovine and mouse cDNA clones were isolated and sequenced. The deduced amino acid sequences showed that the mouse 23 kDa protein is 91% identical to the bovine protein, and is the same as S-modulin, the CAR (cancer-associated retinopathy) protein and recoverin, the Ca(2+)-dependent activator of photoreceptor guanylate cyclase. The amino acid sequence reveals two Ca2+ binding sites, no internal repeats, 59% homology to the chicken visinin protein and 40% homology to calmodulin while Northern analysis demonstrated a single 1.0 kb mRNA species in bovine and mouse retina.
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PMID:Cloning and sequencing of the 23 kDa mouse photoreceptor cell-specific protein. 138 25

The deduced amino acid sequence of the recently cloned mouse 23kD photoreceptor cell-specific protein showed it to be identical to the recoverin protein and the CAR (cancer-associated retinopathy) protein. DNA sequence variants were found in the mouse recoverin gene (Rcvrn), and segregation analysis of restriction fragment length variants in recombinant inbred strains of mice assigned Rcvrn to mouse Chromosome (Chr) 11, between Sparc (3.7 map units) and Zfp-3 (2.3 map units). These results demonstrate a close linkage of recoverin to the tumor suppressor gene, Trp53. On the basis of these data, knowledge of the function of recoverin, and the characteristics of CAR, an experimentally testable model is presented to explain the molecular basis for CAR.
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PMID:Chromosomal assignment of the recoverin gene and cancer-associated retinopathy. 842 1

Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy ("CAR"-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). Among 16 patients with CRMP-5-IgG and optic neuritis (aged 52-74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR-IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4(+) (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7-32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP-5-IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8(+) T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small-cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity. In summary, CRMP-5-IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer.
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PMID:Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. 1283 19

Autoantibodies against recoverin, a Ca2+-binding protein found in patients with cancer-associated retinopathy (CAR syndrome), penetrate retinal cells and induce their apoptosis via a mitochondrial pathway. The goal of this study was to investigate whether the entry of anti-recoverin antibody into E1A.NR3 retinal cells causes a change in intracellular Ca2+. Intracellular Ca2+ was measured using the Ca2+-sensitive fluorescent dye Fura-2 AM in living E1A.NR3 retinal cells treated with anti-recoverin antibody Rec-1, patients' autoantibodies, and control rat and human IgG. The exposure of retinal cells to Rec-1 antibody and to the CAR patients' autoantibodies in vitro caused a significant increase in intracellular Ca2+, while non-specific antibodies did not induce such an effect. Co-treatment of the E1A.NR3 cells with Rec-1 in the presence of nifedipine, a L-type Ca2+ channel blocker, significantly suppressed the increase of Ca2+. Treatment with nifedipine also blocked changes in the anti-apoptotic protein bcl-xL and in expressions of the pro-apoptotic protein bax. Nifedipine-treated cells also showed a decrease in cytosolic cytochrome c release and a decrease in caspase 3 activation, compared to cells treated only with Rec-1 antibody. The increase in the antibody-induced Ca2+ is at least in part dependent on extracellular Ca2+. Nifedipine was found to inhibit the entry of Ca2+ into the cells and to protect them from Rec-1-induced apoptosis. Increased levels of intracellular Ca2+ may lead to retinal dysfunction and degeneration in the CAR syndrome. Our results provide a molecular basis for the use of Ca2+ blockers in the treatment of the CAR syndrome.
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PMID:Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells. 1642 15