Biomedical subjects

Tadashi Yoshida

Publications and source records attributed to Tadashi Yoshida.

At least 19 recordsLinked to original sources

PubMed2007

Distinctly different sensitivity in the induction and reversal of anergy of Th1 and Th2 cells.

T cell anergy is one of the mechanisms of immunological tolerance. We examined in this study the distinct responses of Th1 and Th2 cells to in vitro anergic stimulation using Th1 and Th2 cells from two strains of T cell receptor transgenic mice. Proliferation of the Th2 cells was difficult to suppress by anergic stimulation, while that of Th1 cells was significantly inhibited even by weak stimulation. However, IL-4 production by Th2 cells was definitely reduced by anergic stimulation, although the inhibition level of IL-4 was lower than that of IFN-gamma production by Th1 cells. We also examined the reversal of anergy in both subsets. While both the anergized Th1 and Th2 cells responded to IL-2 stimulation, only the anergy of the Th2 cells could be reversed. This result indicates that progression of the cell cycle was not sufficient for anergy reversal in Th1 cells. Our findings indicate that the induction and reversal of T cell anergy might be affected by the distinct signaling features of Th1 and Th2 cells.

Animals↗

PubMed2006

Regulatory effect of amino acids on the pasting behavior of potato starch is attributable to its binding to the starch chain.

The binding of an amino acid, glycine (Gly), alanine (Ala), epsilon-aminocaproic acid (-AC), monosodium glutamate (GluNa), or lysine (Lys), to starch was examined by a biomolecular interaction analyzer (IAsys). A starch sample (ATS) hydrolyzed to an extent of 1% hydrolysis rate with 15% sulfuric acid was used as a model starch for the binding examination. The reducing end of ATS was oxidized by the Somogyi reagent, and the conversion of the reducing end to the carboxyl group of ATS was confirmed by a carboxylic acid fluorescence labeling reagent. The oxidized ATS was immobilized to the amino group of a sensor cuvette by using water-soluble carbodiimide and N-hydroxysuccinimide through an amide bond. The IAsys examination showed that Gly, Ala, and epsilon-AC scarcely bound to the immobilized starch chains but that GluNa and Lys favorably bound with their increasing concentrations. The relative binding index (RBI) of each amino acid was defined by the ratio of the slope of the linear regression equation between the binding response and the concentration for each amino acid to that for Gly. Because the relationships between the RBI and the pasting characteristics (pasting temperature, peak viscosity, breakdown, and swelling index) could each be expressed by a linear regression equation with a high correlation coefficient, it is concluded that the regulation of the pasting behavior of starch with an amino acid is caused by binding of the amino acid to the starch chains.

Amino Acids↗

PubMed2006

Oral administration of alginic acid oligosaccharide suppresses IgE production and inhibits the induction of oral tolerance.

We have found that alginic acid oligosaccharide (ALGO) enhanced Th1 by promoting IL-12 production, suggesting that ALGO can be applied as an anti-allergic food. In this study we examined both positive and negative functions of ALGO. First we investigated the anti-allergic activity of ALGO, as a positive function, when orally administered. IgE production was significantly inhibited in mice fed ALGO as compared to control mice. This result indicates that ALGO had anti-allergic activity even when orally administered. On the other hand, we also found a negative function of ALGO. Oral co-administration of a protein antigen and ALGO inhibited the induction of oral tolerance to the protein. These data indicate the potential of ALGO as an anti-allergic food material and the necessity of further examination to determine a safe method application.

Administration, Oral↗

PubMed2006

1H NMR Study of the influence of hemin vinyl-->methyl substitution on the interaction between the C-terminus and substrate and the "aging" of the heme oxygenase from Neisseria meningitidis: induction of active site structural heterogeneity by a two-fold symmetric hemin.

Solution 1H NMR has been used to characterize the active site molecular and electronic structure of the cyanide-inhibited 2,4-dimethyldeuterohemin complex of the heme oxygenase from Neisseria meningitidis (NmHO) with respect to the mode of interaction of the C-terminus with the substrate and the spontaneous "aging" of NmHO that results in the cleavage of the C-terminal Arg208-His209 dipeptide. The structure of the portion involving residues Ala12-Phe192 is found to be essentially identical to that of the protohemin complex in either solution or crystal. However, His207 from the C-terminus is found to interact strongly with the substrate 1CH3, as opposed to the 8CH3 in the protohemin complex. The different mode of interaction of His207 with the alternate substrates is attributed to the 2-vinyl group of protohemin sterically interfering with the optimal orientation of the proximal helix Asp27 carboxylate that serves as acceptor to the strong H-bond by the peptide of His207. The 2,4-dimethyldeuterohemin HO complex "ages" in manner similary to that of protohemin, (Liu, Y., Ma, L.-H., Satterlee, J.D., Zhang, X., Yoshida, T., and La Mar, G. N., (2006) Biochemistry 45, 3875-3886) with mass spectrometry and N-terminal sequencing indicating that the Arg208-His209 dipeptide is cleaved. The 2,4-dimethyldeuterohemin complex of WT HO populates an equilibrium isomer stabilized in low phosphate concentration for which the axial His imidazole ring is rotated by approximately 20 degrees from that in the WT. The His ring reorientation is attributed to Asp24 serving as the H-bond acceptor to the His207 peptide NH, rather than to the His23 ring NdeltaH as in the crystals. The functional implications of the altered C-terminal interaction with substrate modification are discussed.

Binding Sites↗

PubMed2006

Spectroscopic characterization of a higher plant heme oxygenase isoform-1 from Glycine max (soybean)--coordination structure of the heme complex and catabolism of heme.

Heme oxygenase converts heme into biliverdin, CO, and free iron. In plants, as well as in cyanobacteria, heme oxygenase plays a particular role in the biosynthesis of photoreceptive pigments, such as phytochromobilins and phycobilins, supplying biliverdin IX(alpha) as a direct synthetic resource. In this study, a higher plant heme oxygenase, GmHO-1, of Glycine max (soybean), was prepared to evaluate the molecular features of its heme complex, the enzymatic activity, and the mechanism of heme conversion. The similarity in the amino acid sequence between GmHO-1 and heme oxygenases from other biological species is low, and GmHO-1 binds heme with 1 : 1 stoichiometry at His30; this position does not correspond to the proximal histidine of other heme oxygenases in their sequence alignments. The heme bound to GmHO-1, in the ferric high-spin state, exhibits an acid-base transition and is converted to biliverdin IX(alpha) in the presence of NADPH/ferredoxin reductase/ferredoxin, or ascorbate. During the heme conversion, an intermediate with an absorption maximum different from that of typical verdoheme-heme oxygenase or CO-verdoheme-heme oxygenase complexes was observed and was extracted as a bis-imidazole complex; it was identified as verdoheme. A myoglobin mutant, H64L, with high CO affinity trapped CO produced during the heme degradation. Thus, the mechanism of heme degradation by GmHO-1 appears to be similar to that of known heme oxygenases, despite the low sequence homology. The heme conversion by GmHO-1 is as fast as that by SynHO-1 in the presence of NADPH/ferredoxin reductase/ferredoxin, thereby suggesting that the latter is the physiologic electron-donating system.

Amino Acid Sequence↗

PubMed2006

Reduced immunogenicity of beta-lactoglobulin by conjugating with chitosan.

Bovine beta-lactoglobulin (beta-LG) was conjugated with chitosan (CHS) by means of a water-soluble carbodiimide to reduce the immunogenicity of beta-LG. Each beta-LG-CHS conjugate was purified by ion-exchange chromatography and hydrophobic chromatography. The conjugation between beta-LG and CHS was confirmed by SDS-PAGE, the isoelectric point of the conjugate being higher than that of beta-LG. Two types of the beta-LG-CHS conjugate were obtained with molar ratios of beta-LG to CHS of 1:1 (F1) and 1:2 (F2). Structural analyses by fluorescence measurement, ELISA with monoclonal antibodies and retinol-binding activity indicated that the conjugates had almost maintained the native structure of beta-LG. The antigenicity of the beta-LG-CHS conjugates was similar to that of beta-LG in C3H/He mice. Reduction of the immunogenicity of beta-LG was achieved by conjugation with CHS. In particular, F2 showed very low immunogenicity. B cell epitopes of beta-LG and the conjugates recognized in C3H/He mice were determined with 15-mer multi-pin peptide; the linear epitope profiles of the conjugates were found to be similar to those of beta-LG, while the antibody response to each epitope was dramatically reduced. Conjugation of beta-LG with chitosan was effective for reducing the immunogenicity of beta-LG.

Animals↗

PubMed2006

Concise review: epigenetic mechanisms contribute to pluripotency and cell lineage determination of embryonic stem cells.

Epigenetic mechanisms, such as histone modifications and DNA methylation, have been shown to play a key role in the regulation of gene transcription. Results of recent studies indicate that a novel "bivalent" chromatin structure marks key developmental genes in embryonic stem cells (ESCs), wherein a number of untranscribed lineage-control genes, such as Sox1, Nkx2-2, Msx1, Irx3, and Pax3, are epigenetically modified with a unique combination of activating and repressive histone modifications that prime them for potential activation (or repression) upon cell lineage induction and differentiation. However, results of these studies also showed that a subset of lineage-control genes, such as Myf5 and Mash1, were not marked by these histone modifications, suggesting that distinct epigenetic mechanisms might exist for lineage-control genes in ESCs. In this review article, we summarize evidence regarding possible mechanisms that control these unique histone modifications at lineage-control gene loci in ESCs and consider their possible contribution to ESC pluripotency. In addition, we propose a novel "histone modification pulsing" model wherein individual pluripotent stem cells within the inner cell mass of blastocysts undergo transient asynchronous histone modifications at these developmental gene loci, thereby conferring differential responsiveness to environmental cues and morphogenic gradients important for cell lineage determination. Finally, we consider how these rapid histone modification exchanges become progressively more stable as ESCs undergo differentiation and maturation into specialized cell lineages.

Animals↗

PubMed2006

Platelet-derived growth factor-BB represses smooth muscle cell marker genes via changes in binding of MKL factors and histone deacetylases to their promoters.

A hallmark of smooth muscle cell (SMC) phenotypic switching is suppression of SMC marker gene expression. Although myocardin has been shown to be a key regulator of this process, the role of its related factors, MKL1 and MKL2, in SMC phenotypic switching remains unknown. The present studies were aimed at determining if: 1) MKL factors contribute to the expression of SMC marker genes in cultured SMCs; and 2) platelet-derived growth factor-BB (PDGF-BB)-induced repression of SMC marker genes is mediated by suppression of MKL factors. Results of gain- and loss-of-function experiments showed that MKL factors regulated the expression of single and multiple CArG [CC(AT-rich)(6)GG]-containing SMC marker genes, such as smooth muscle (SM) alpha-actin and telokin, but not CArG-independent SMC marker genes such as smoothelin-B. Treatment with PDGF-BB reduced the expression of CArG-containing SMC marker genes, as well as myocardin expression in cultured SMCs, while it had no effect on expression of MKL1 and MKL2. However, of interest, PDGF-BB induced the dissociation of MKL factors from the CArG-containing region of SMC marker genes, as determined by chromatin immunoprecipitation assays. This dissociation was caused by the competition between MKL factors and phosphorylated Elk-1 at early time points, but subsequently by the reduction in acetylated histone H4 levels at these promoter regions mediated by histone deacetylases, HDAC2, HDAC4, and HDAC5. Results provide novel evidence that PDGF-BB-induced repression of SMC marker genes is mediated through combinatorial mechanisms, including downregulation of myocardin expression and inhibition of the association of myocardin/MKL factors with CArG-containing SMC marker gene promoters.

Actins↗

PubMed2006

Effect of sorbed water on the thermal stability of soybean protein.

A soybean protein isolate (SPI), and its beta-conglycinin and glycinin componets were obtained from defatted soybean flour by applying dissolution and precipitation based on the difference in their solubility depending on each isoelectric point. The purity evaluated by SDS-PAGE of the beta-conglycinin and glycinin preparations was about 84% and 80%, respectively, resulting in a clear difference in the pH dependence on solubility. A BET plot derived from the water sorption isotherm at 25 degrees C showed that the amount of the monolayer adsorption of these preparations was about 6-9%, the value for the beta-conglycinin preparation being about 1.5 times higher than that for the glycinin preparation. The beta-conglycinin and glycinin preparations were respectively denatured at around 75 degrees C and 86 degrees C in the presence of excess water, whereas the denaturation temperature of both preparations was markedly increased by decreasing sorbed water content below 40%, corresponding well with the unfrozen water content.

Adsorption↗

PubMed2006

13C and 15N NMR studies of iron-bound cyanides of heme proteins and related model complexes: sensitive probe for detecting hydrogen-bonding interactions at the proximal and distal sides.

Studies of the 13C and 15N NMR paramagnetic shifts of the iron-bound cyanides in the ferric cyanide forms of various heme proteins containing the proximal histidine and related model complexes are reported. The paramagnetic shifts of the 13C and 15N NMR signals of the iron-bound cyanide are not significantly affected by the substitution of the porphyrin side chains. On the other hand, the paramagnetic shifts of both the 13C and 15N NMR signals decrease with an increase in the donor effect of the proximal ligand, and the 13C NMR signal is more sensitive to a modification of the donor effect of the proximal ligand than the 15N NMR signal. With the tilt of the iron-imidazole bond, the paramagnetic shift of the 13C NMR signal increases, whereas that of the 15N NMR signal decreases. The hydrogen-bonding interaction of the iron-bound cyanide with a solvent decreases the paramagnetic shift of both 13C and 15N NMR signals, and the effect is more pronounced for the 15N NMR signal. Data on the 13C and 15N NMR signals of iron-bound cyanide for various heme proteins are also reported and analyzed in detail. Substantial differences in the 13C and 15N NMR shifts for the heme proteins can be explained on the basis of the results for the model complexes and structures around the heme in the heme proteins. The findings herein show that the paramagnetic shift of the 13C NMR signal of the iron-bound cyanide is a good probe to estimate the donor effect of the proximal imidazole and that the ratio of 15N/13C NMR shifts allows the hydrogen-bonding interaction on the distal side to be estimated.

Carbon Isotopes↗

PubMed2006

Hypoxia reduces the expression of heme oxygenase-2 in various types of human cell lines. A possible strategy for the maintenance of intracellular heme level.

Heme oxygenase consists of two structurally related isozymes, heme oxygenase-1 and and heme oxygenase-2, each of which cleaves heme to form biliverdin, iron and carbon monoxide. Expression of heme oxygenase-1 is increased or decreased depending on cellular microenvironments, whereas little is known about the regulation of heme oxygenase-2 expression. Here we show that hypoxia (1% oxygen) reduces the expression levels of heme oxygenase-2 mRNA and protein after 48 h of incubation in human cell lines, including Jurkat T-lymphocytes, YN-1 and K562 erythroleukemia, HeLa cervical cancer, and HepG2 hepatoma, as judged by northern blot and western blot analyses. In contrast, the expression level of heme oxygenase-1 mRNA varies under hypoxia, depending on the cell line; it was increased in YN-1 cells, decreased in HeLa and HepG2 cells, and remained undetectable in Jurkat and K562 cells. Moreover, heme oxygenase-1 protein was decreased in YN-1 cells under the conditions used, despite the induction of heme oxygenase-1 mRNA under hypoxia. The heme oxygenase activity was significantly decreased in YN-1, K562 and HepG2 cells after 48 h of hypoxia. To explore the mechanism for the hypoxia-mediated reduction of heme oxygenase-2 expression, we showed that hypoxia shortened the half-life of heme oxygenase-2 mRNA (from 12 h to 6 h) in YN-1 cells, without affecting the half-life of heme oxygenase-1 mRNA (9.5 h). Importantly, the heme contents were increased in YN-1, HepG2 and HeLa cells after 48 h of incubation under hypoxia. Thus, the reduced expression of heme oxygenase-2 may represent an important adaptation to hypoxia in certain cell types, which may contribute to the maintenance of the intracellular heme level.

Acclimatization↗

PubMed2006

Oral administration of IL-12 abrogates the induction but not the maintenance of oral tolerance.

BACKGROUND: IL-12 is a Th1-inducing cytokine and known to be induced by some food factors. This function of such foods is expected to be applied for antiallergic materials. However, the influence of IL-12 on the immune responses has not been fully investigated. Oral tolerance is an immunologically unresponsive state induced by orally administered food antigens. Although a failure in the induction of oral tolerance would result in food allergy, the mechanisms for the induction and abrogation of oral tolerance have not been clarified. IL-12 induced by food factors may also affect the induction of oral tolerance. In this study we examined the effect of the oral administration of IL-12 on the induction and maintenance of oral tolerance. METHODS: BALB/c mice were fed beta-lactoglobulin with or without IL-12. After immunizing them with the antigen, the serum antibody titer of these mice was measured to evaluate the induction of oral tolerance. RESULTS: The induction of oral tolerance was prevented in the mice that had been simultaneously fed the antigen and IL-12. On the other hand IL-12 did not abrogate the already established oral tolerance when it was administered after feeding the antigen. We also found that oral tolerance could be induced normally in mice that had failed to induce such tolerance by simultaneous feeding of IL-12 and the antigen. CONCLUSIONS: The results indicate that IL-12 induced in the intestine by some food factors is involved in the regulation of oral tolerance.

Administration, Oral↗

PubMed2006

1H NMR study of the magnetic properties and electronic structure of the hydroxide complex of substrate-bound heme oxygenase from Neisseria meningitidis: influence of the axial water deprotonation on the distal H-bond network.

The substrate and active site residues of the low-spin hydroxide complex of the protohemin complex of Neisseria meningitidis heme oxygenase (NmHO) have been assigned by saturation transfer between the hydroxide and previously characterized aquo complex. The available dipolar shifts allowed the quantitation of both the orientation and anisotropy of the paramagnetic susceptibility tensor. The resulting positive sign, and reduced magnitude of the axial anisotropy relative to the cyanide complex, dictate that the orbital ground state is the conventional "d(pi)" (d(2)(xy)(d(xz), d(yz))(3)); and not the unusual "d(xy)" (d(2)(xz)d(2)(yz)d(xy)) orbital ground state reported for the hydroxide complex of the homologous heme oxygenase (HO) from Pseudomonas aeruginosa (Caignan, G.; Deshmukh, R.; Zeng, Y.; Wilks, A.; Bunce, R. A.; Rivera, M. J. Am. Chem. Soc. 2003, 125, 11842-11852) and proposed as a signature of the HO distal cavity. The conservation of slow labile proton exchange with solvent from pH 7.0 to 10.8 confirms the extraordinary dynamic stability of NmHO complexes. Comparison of the diamagnetic contribution to the labile proton chemical shifts in the aquo and hydroxide complexes reveals strongly conserved bond strengths in the distal H-bond network, with the exception of the distal His53 N(epsilon)(1)H. The iron-ligated water is linked to His53 primarily by a pair of nonligated, ordered water molecules that transmit the conversion of the ligated H-bond donor (H(2)O) to a H-bond acceptor (OH(-)), thereby increasing the H-bond donor strength of the His53 side chain.

Anisotropy↗

PubMed2006

Modulation of the axial water hydrogen-bonding properties by chemical modification of the substrate in resting state, substrate-bound heme oxygenase from Neisseria meningitidis; coupling to the distal H-bond network via ordered water molecules.

The hydrogen bonding of ligated water in ferric, high-spin, resting-state substrate complexes of heme oxygenase from Neisseria meningitidis has been systematically perturbed by variable electron-withdrawing substituents on the hemin periphery. The pattern of 1H NMR-detected dipolar shifts due to the paramagnetic anisotropy is strongly conserved among the four complexes, with the magnitude of dipolar shifts or anisotropy increasing in the order of substituent formyl < vinyl < methyl. The magnetic anisotropy is axial and oriented by the axial Fe-His23 bond, and while individual anisotropies have uncertainties of approximately 5%, the relative values of deltachi (and the zero-field splitting constant, D proportional, variant deltachi(ax)) are defined to 1%. The unique changes in the axial field strength implied by the variable zero-field splitting are in accord with expectations for the axial water serving as a stronger H-bond donor in the order of hemin substituents formyl > vinyl > methyl. These results establish the axial anisotropy (and D) as a sensitive probe of the H-bonding properties of a ligated water in resting-state, substrate complexes of heme oxygenase. Correction of observed labile proton chemical shifts for paramagnetic influences indicates that Gln49 and His53, some approximately 10 angstroms from the iron, sense the change in the ligated water H-bonding to the three nonligated ordered water molecules that link the two side chains to the iron ligand. The present results augur well for detecting and characterizing changes in distal water H-bonding upon mutagenesis of residues in the distal network of ordered water molecules and strong H-bonds.

Anisotropy↗

PubMed2006

Characterization of the spontaneous "aging" of the heme oxygenase from the pathological bacterium Neisseria meningitidis via cleavage of the C-terminus in contact with the substrate. Implications for functional studies and the crystal structure.

Solution 1H NMR spectroscopy and mass spectrometry are utilized to characterize the irreversible "aging" of native heme oxygenase from N. meningitidis, NmHO. 2D NMR characterization of the cyanide-inhibited substrate complex shows that the C-terminal interaction between Arg208His209 and the exposed pyrrole of the protohemin substrate in the "native" NmHO complex is lost in the "aging". Mass spectrometry and N-terminal sequencing of wild type and "aged" NmHO reveal that the "aging" process involves cleavage of the Arg208His209 dipeptide. The construction of the double deletion mutant without Arg208His209 and its NMR comparison as both the resting state substrate complex and its cyanide-inhibited complex with the "aged" NmHO reveal that cleavage of the C-terminal dipeptide is the only modification during the aging. Comparison of cyanide ligand binding constants reveal a factor approximately 1.7 greater CN- affinity in the native than "aged" NmHO. The rate of protohemin degradation and its stereoselectivity are unaffected by the C-terminal truncation. However, the free alpha-biliverdin yield in the presence of desferrioxamine is significantly increased in the "aged" NmHO and its deletion mutant relative to WT, arguing for a role of the NmHO C-terminus in modulating product release. The facile cleavage of Arg208His209 in the resting state complex, with a half-life of approximately 24 h at 25 degrees C, suggests that previous characterization of NmHO may have been carried out on a mixture of native and "aged" NmHO, and may account for the "lost" C-terminal residues in the crystal structures.

Base Sequence↗

PubMed2006

Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase.

Human indoleamine 2,3-dioxygenase (IDO) catalyzes the cleavage of the pyrrol ring of L-Trp and incorporates both atoms of a molecule of oxygen (O2). Here we report on the x-ray crystal structure of human IDO, complexed with the ligand inhibitor 4-phenylimidazole and cyanide. The overall structure of IDO shows two alpha-helical domains with the heme between them. A264 of the flexible loop in the heme distal side is in close proximity to the iron. A mutant analysis shows that none of the polar amino acid residues in the distal heme pocket are essential for activity, suggesting that, unlike the heme-containing monooxygenases (i.e., peroxidase and cytochrome P450), no protein group of IDO is essential in dioxygen activation or proton abstraction. These characteristics of the IDO structure provide support for a reaction mechanism involving the abstraction of a proton from the substrate by iron-bound dioxygen. Inactive mutants (F226A, F227A, and R231A) retain substrate-binding affinity, and an electron density map reveals that 2-(N-cyclohexylamino)ethane sulfonic acid is bound to these residues, mimicking the substrate. These findings suggest that strict shape complementarities between the indole ring of the substrate and the protein side chains are required, not for binding, but, rather, to permit the interaction between the substrate and iron-bound dioxygen in the first step of the reaction. This study provides the structural basis for a heme-containing dioxygenase mechanism, a missing piece in our understanding of heme chemistry.

Amino Acid Sequence↗

PubMed2006

Crystallization and preliminary crystallographic studies of human indoleamine 2,3-dioxygenase.

Indoleamine 2,3-dioxygenase (IDO) is a haem-containing dioxygenase that catalyzes the oxidative cleavage of the pyrrole ring of indoleamines by the insertion of molecular oxygen. This reaction is the first and the rate-limiting step in the kynurenine pathway, the major Trp catabolic pathway in mammals. Recombinant human IDO was crystallized by the vapour-diffusion technique. The addition of 4-phenylimidazole as a haem ligand was essential for crystallization. The crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 86.1, b = 98.0, c = 131.0 A. Diffraction data were collected to 2.3 A resolution.

Crystallization↗

PubMed2006

Telomere length of normal leukocytes is affected by a functional polymorphism of hTERT.

Transcriptional regulation of human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is essential for telomerase activity associated with telomere length. In this study, we investigated the effects of a (-1327)T/C polymorphism within the hTERT promoter region on the hTERT promoter activity and leukocyte telomere length in normal individuals. The promoter activity in the (-1327)T-sequence was significantly higher than that in the (-1327)C-sequence (p = 0.0004). For leukocyte telomere length, the (-1327)T-allele carriers had significantly longer than the (-1327)T-allele non-carriers (p = 0.0007). Also, there was no age-related shortening in leukocyte telomere length in the (-1327)T/T (p = 0.6633) and (-1327)T/C subjects (p = 0.1691), whereas there was clear age-related telomere shortening in the (-1327)C/C subjects (p = 0.0117). These findings suggest that the functional (-1327)T/C polymorphism of hTERT is associated with leukocyte telomere length in normal individuals.

Base Sequence↗