Disease relevance of INA

• alpha-internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease [1].
• The results strongly support the view that alpha-internexin is a fourth subunit of neurofilaments in the adult CNS, providing a basis for its close relationship with neurofilaments in CNS diseases associated with neurofilament accumulation [2].
• Northern analysis revealed that three additional genes, ASCL1, INA, and SV2B are expressed in LuCaP 49 but not in various prostate cancer cell lines or xenografts [3].
• However, the ratio between factor XI and C1-INA activity was significantly higher than in normal and urticaria patients [4].
• Interaction between C1-INA, coagulation, fibrinolysis and kinin system in hereditary angioneurotic edema (HANE) and urticaria [4].

Psychiatry related information on INA

• Small subsets of abnormal neuronal inclusions in Alzheimer's disease, Lewy body diseases, and motor neuron disease also contain epitopes of alpha-internexin [5].
• Therefore, to determine the specificity of this protein, alpha-internexin immunohistochemistry was undertaken on cases of NIFID, non-tau frontotemporal dementias, motor neuron disease, alpha-synucleinopathies, tauopathies, and normal aged control brains [5].

High impact information on INA

• Using the yeast two-hybrid system, we have identified a specific Tax-binding protein as the neuronal specific intermediate filament protein, alpha-internexin [6].
• This in vivo interaction also resulted in a dramatic reduction in Tax transactivation and the network formation by alpha-internexin [6].
• Other neuronal intermediate filament proteins (alpha-internexin, peripherin) also accumulated in these spheroids [7].
• The immunohistological findings common to all cases are alpha-internexin and neurofilament-positive neuronal cytoplasmic inclusions, which have not been found in comparable density in other neurodegenerative disorders [8].
• alpha-Internexin is a 66 kDa protein that copurifies with intermediate filaments (IF) from rat spinal cord and optic nerve [9].

Chemical compound and disease context of INA

• Our data suggest that hypoxia extensively remodels the signaling pathway by switching off tyrosine phosphorylation of some cellular components (i.e., alpha-internexin) and switching on tyrosine phosphorylation of some other proteins (i.e., heat shock cognate 70, aconitase, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and pyruvate kinase) [10].

Biological context of INA

• The novel antigen 018INX was derived from a small open reading frame in a region of alpha-internexin mRNA that was previously described as 3' untranslated region [11].
• Both the DNA and the predicted amino acid sequences showed a high degree of homology to the rat NF-66 [12].
• By labelling the INA fusion proteins with iodinated antibody it was found that molecules with either endocytosis signal were expressed at the plasma membrane and internalized rapidly [13].
• Membrane-bound INA can be indirectly activated by energy transfer from visible chromophores [14].
• These different activation domains have been shown previously to differ in their ability to activate an artificial test promoter containing a Brn-3a binding site and the naturally occurring alpha-internexin gene promoter [15].

Anatomical context of INA

• The discovery of alpha-internexin in the cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and other neurological diseases with pathological accumulations of IFs [1].
• Furthermore, fluorescence-activated cell sorter analysis revealed that approximately 16% of U937 cells carry C1-INA as a surface bound antigen [16].
• In this report we demonstrate that the human monocyte-like cell line U937 is also capable of synthesizing functional C1-INA [16].
• Human monocytes are known to synthesize many of the components of complement, including C1-INA [16].
• Ii is known to form trimers and when INA was transfected into COS cells it assembled as a tetramer like NA [13].

Associations of INA with chemical compounds

• Synthesis of C1 inhibitor (C1-INA) by a human monocyte-like cell line, U937 [16].
• The capacity of INA at low concentrations to uncouple the hormone receptor from the adenylate cyclase is not restricted to the LH/hCG receptor [17].
• Of these molecules only the 20-kDa T3 antigen could be labeled with the hydrophobic reagent 5-iodonaphthyl-1-azide (INA) [18].
• That the uncoupling of the receptor from the enzyme by INA occurred within the lipid bilayer can be derived from the finding that the prior presence neither of saturating concentrations of hCG nor of the aqueous nitrene-scavenger glutathione (GSH) prevented this effect [17].
• Photolysis at higher concentrations of INA (0.1-1 mM) led to the inhibition of the adenylate cyclase stimulated by fluoride [17].

Other interactions of INA

• RNase protection assay indicated that NF-66 was expressed in human fetal brain as early as the 16th gestational week [12].
• Expression of marker proteins including beta-III-tubulin, alpha-internexin, NF-L and NF-M, tau and L1 indicated the neurons were differentiated, and in some cases polarized [19].
• Exercise also up-regulated specific synaptic-plasticity-related proteins, the cytoskeletal protein alpha-internexin and molecular chaperones (chaperonin-containing TCP-1, neuronal protein 22, heat shock 60-kDa protein 1 and heat shock protein 8) [20].
• ASCL1, INA, and SV2B are potential molecular markers for small cell NE tumors and NE cells of the prostate [3].
• The AHP adopted the method of NSF-INA for inclusion in the AHP monograph owing to observed superiority of this method in terms of precision, glycoside calculation, ease of sample preparation and chromatographic parameters [21].

Analytical, diagnostic and therapeutic context of INA

• We raised 2 highly specific monoclonal antibodies to alpha-internexin which were applied to frozen rat brain sections and Western blots of cytoskeletal extracts [9].
• Alpha-internexin exhibits transport and turnover rates identical to those of triplet proteins in optic axons and colocalizes with NF-M on single neurofilaments by immunogold electron microscopy [2].
• Data from the ELISA indicate that U937 cells contain between 2.1 to 12.8 ng of C1-INA per 1 X 10(6) cells [16].
• In NHANES III, rate INA values (x) can be transformed to WHO-IFCC Reference Material-based values (y) as follows: for apoA-I, y = 0.87x + 251.8 mg/L (r = 0.93, SEslope = 0.13, SEintercept = 17, n = 708); for apoB (mg/L), y = 1.068x + 112.8 mg/L (r = 0.98, SEslope = 0.08, SEintercept = 7, n = 646) [22].
• We evaluated new, commercially available reagents for assaying apolipoproteins (apo) A-I and B by rate nephelometry (INA) [23].

References