Disease relevance of OLFM1

• In a temporal series of 29 Down syndrome (DS) brains from patients aged 12 to 73 years, the earliest AMY IR was detected in some plaques at age 15, following the earliest appearance of Abeta plaques (age 12 years), and then accrued within a subset of Abeta deposits, namely, the more spherical, compacted plaques [1].
• Recent evidence has revealed that a highly sensitive and specific guanine nucleotide regulatory process controls intracellular Ca2+ release within N1E-115 neuroblastoma cells (Gill, D. L., Ueda, T., Chueh, S. H., and Noel, M. W. (1986) Nature 320, 461-464) [2].
• The lowest observed effect level (LOEL) and the no observed effect level (NOEL) of peroxisome proliferation in the rat, as determined by the induction of specific enzymes (peroxisomal beta-oxidation, carnitine-acetyl-transferase, cytochrome P-452), DNA synthesis, and hepatomegaly, may be assumed as 50 and 25 mg/kg b.w. per day, respectively [3].
• Group 2 genes are normally down-regulated during the window of implantation but are significantly increased with endometriosis: semaphorin E, neuronal olfactomedin-related endoplasmic reticulum localized protein mRNA and Sam68-like phosphotyrosine protein alpha [4].
• Systemic toxicity is considered in respect to possible improved ways of determining the "NOEL," that is, the no-observed-effect level [5].

Psychiatry related information on OLFM1

• Novel plaque-like "AMY" lesions were recently described in the brains of patients with Alzheimer's disease (AD) [1].
• Paap and Noel revisited: individual differences in independent word recognition tasks in relation to the dual-task paradigm [6].

High impact information on OLFM1

• Molecular cloning of olfactomedin, an extracellular matrix protein specific to olfactory neuroepithelium [7].
• Olfactomedin is expressed exclusively in olfactory neuroepithelium and its amino acid sequence shows no homologies to any known protein [7].
• By analogy to other extracellular matrix proteins of the nervous system, olfactomedin may influence the maintenance, growth, or differentiation of chemosensory cilia on the apical dendrites of olfactory neurons [7].
• Another olfactomedin-related protein, known as noelin or pancortin, is involved in the generation of neural crest cells [8].
• However, unlike noelin, rat optimedin is also highly expressed in the epithelial cells of the iris and the ciliary body in close proximity to the sites of Myoc expression [8].

Chemical compound and disease context of OLFM1

• The NOEL for exposure via the oral route was 1 mg/kg body weight/day, with exposures above this causing neurotoxic effects in animals [9].
• The JECFA group considered that the small body weight reduction in the F2 pups of the highest dose group prevented this from being regarded as a no adverse effect level, and so allocated an ADI for curcumin of 0-3mg/kg bw based on the intake of 250-320mg/kg bw in the mid-dose group as the NOEL [10].
• Based on available toxicity data and derived NOEL, lasalocid was less toxic than all ionophores except salinomycin [11].
• The no observed effect levels (NOEL) of o-Cresol was 240 mg/kg in mink and 778 mg/kg in ferrets in short-term feeding studies, with no significant dose-related toxicity (excluding body weight parameters) [12].
• In acute toxicity studies, atrazine caused developmental toxicity in the rabbit [no observed effect level (NOEL) 5 mg kg(-1) day(-1)] and cardiotoxicity in a dog chronic study (NOEL 0.5 mg kg(-1) day(-1)); cancer (mammary glands) resulted from lifetime exposure [13].

Biological context of OLFM1

• Here we describe the identification of a novel olfactomedin-related gene, named optimedin, located on chromosome 1p21 in humans [8].
• Re: A.C. Noël et al., Invasion of reconstituted basement membrane matrix is not correlated to the malignant metastatic cell phenotype. Cancer Res., 51:405-414, 1991 [14].
• TIGR cDNA encodes an olfactomedin-related glycoprotein of 504 amino acids with motifs for N- and O-linked glycosylation, glycosaminoglycan initiation, hyaluronic acid binding, and leucine zippers [15].
• Transfection of isl-1-depleted isl-1 (AS)InR1 -G9 cell lines demonstrated that the E2 element continued to repress thymidine kinase promoter activity, whereas the positive transcriptional activity mediated by the AMY element was considerably reduced in isl-1 (AS)-InR1-G9 cell lines [16].
• The three-dimensional structure of CHS [Ferrer, J.-L., Jez, J. M., Bowman, M. E., Dixon, R. A., and Noel, J. P. (1999) Nat. Struct. Biol. 6, 775-784] suggests that four residues (Cys164, Phe215, His303, and Asn336) participate in the multiple decarboxylation and condensation reactions catalyzed by this enzyme [17].

Anatomical context of OLFM1

• A sensitive and specific guanine nucleotide regulatory process has recently been shown to rapidly mediate a substantial release of Ca2+ from endoplasmic reticulum within the N1E-115 neuronal cell line (Gill, D. L., Ueda, T., Chueh, S. H., and Noel, M. W. (1986) Nature 320, 461-464) [18].
• Gene structure and properties of TIGR, an olfactomedin-related glycoprotein cloned from glucocorticoid-induced trabecular meshwork cells [15].
• Likewise, LOEL and NOEL of rodent carcinogenesis, that is, 300 and 50 to 100 mg/kg b.w. per day, respectively, are above but not too far from the corresponding values for the investigated parameters of peroxisome proliferation [3].
• The isl-1 homeodomain binds to the AT-rich AMY element (-156 to -137) in the human amylin (hAMY) gene promoter, and electrophoretic mobility shift assay experiments using isl-1 specific antiserum detected the formation of an hAMY-isl-1 complex using nuclear extract from InR1 -G9 islet cells [16].
• Immunohistochemical studies at the light microscopic and electron microscopic level show that olfactomedin is localized in secretory granules of sustentacular cells, in acinar cells of olfactory glands, and at the mucociliary surface [19].

Associations of OLFM1 with chemical compounds

• This interaction depends on the C-terminal olfactomedin domain, but does not require the five well-conserved cysteine residues [20].
• The structural basis for this coupled isomerization-cyclization reaction sequence can be inferred by homology modeling of (-)-4S-limonene synthase based on the three-dimensional structure of the sesquiterpene cyclase epi-aristolochene synthase [Starks, C. M., Back, K., Chappell, J., and Noel, J. P. (1997) Science 277, 1815-1820] [21].
• To study glycosylation of olfactomedin, we raised antibodies against the mature protein and antibodies against a region adjacent to an N-linked glycosylation site near its amino terminus [22].
• BHA-induced proliferative effects, which appear to be critical for the tumorigenic response, show a NOEL at a dose below that yielding benign tumors [23].
• Thus, the present experiment was performed to study the effects of AMY on estrogen deficiency-induced bone loss in rats [24].

Regulatory relationships of OLFM1

• 3. Together, our findings indicate that hGC-1 is primarily expressed as an extracellular olfactomedin-related glycoprotein during normal myeloid-specific lineage differentiation, suggesting the possibility of a matrix-related function for hGC-1 in differentiation [25].

Other interactions of OLFM1

• Results from several laboratories showing defects in the olfactomedin homology domain of the TIGR gene have generated particular interest concerning potential pathogenic mechanisms [26].
• RESULTS: The study led to the identification of three groups of proteins encoded by three different genes; Noelin 1 (9q34.3), Noelin 2 (19p13.2), and Noelin 3 (1p22) encompassing 45,575 bp, 82,679 bp, and 1,93,421 bp of the genomic sequence, respectively [27].
• Identification and characterization of a novel member of olfactomedin-related protein family, hGC-1, expressed during myeloid lineage development [25].
• This cleavage predicts the production of two fragments, one of 35 kDa containing the C-terminal olfactomedin-like domain, and another of 20 kDa containing the N-terminal leucine zipper-like domain [28].
• Additionally, we have identified a group of chitinase sequences containing several of the highly conserved motifs present in the C-terminal region of the olfactomedin domain-containing sequences [29].

Analytical, diagnostic and therapeutic context of OLFM1

• In addition, the expression patterns of genes encoding olfactomedin-domain proteins were analyzed by RT-PCR [30].
• Perfusion with the olfactomedin domain of myocilin does not affect outflow facility [31].
• Olfactomedin strongly binds to Ricinus communis agglutinin I and has been purified to homogeneity by lectin affinity chromatography [19].
• Various authors have discussed the shortcomings of using NOEL and have suggested the use of an estimable effect level determined from a dose-response curve fitted to bioassay data, e.g., the dose at which 1% of the animals are adversely affected, and employing some form of conservative low dose extrapolation to control risks at lower doses [32].
• AMY gene transcripts were detectable by autoradiography in RT-PCR amplified DNA obtained from as little as 5 pg of human pancreatic or parotid total RNA [33].

References