Biomedical subjects

Yong-Sik Kim

Publications and source records attributed to Yong-Sik Kim.

At least 19 recordsLinked to original sources

PubMed2006

8-hydroxydeoxyguanosine suppresses NO production and COX-2 activity via Rac1/STATs signaling in LPS-induced brain microglia.

Free 8-hydroxydeoxyguanosine (oh(8)dG), a nucleoside of 8-hydroxyguanine (oh(8)Gua), present in cytosol is not incorporated into DNA. However, nothing is known about its biological function when it presents in cytosol as a free form. We demonstrate here for the first time that oh(8)dG inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO) production and cyclooxygenase-2 (COX-2) activity, and both gene transcriptions in microglia. Furthermore, oh(8)dG reduced mRNA levels of pro-inflammatory cytokine, such as IL-1beta, IL-6, and TNF-alpha, in activated BV2 cells. We also found that oh(8)dG suppressed reactive oxygen species (ROS) production through reduction of NADPH oxidase activity and blocked Rac1/STATs signal cascade. Finally, oh(8)dG suppressed recruitment of STATs and p300 to the iNOS and COX-2 promoters, and inhibited H3 histone acetylation. Taken together, these results provide new aspects of oh(8)dG as an anti-inflammatory agent.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2006

Membrane depolarization stimulates the proliferation of SH-SY5Y human neuroblastoma cells by increasing retinoblastoma protein (RB) phosphorylation through the activation of cyclin-dependent kinase 2 (Cdk2).

Membrane depolarization causes transmembrane ionic influxes that induce various gene expressions, and is involved in the processes of neuronal differentiation and apoptosis. However, the effect of membrane depolarization on neuronal proliferation has not been established. In this study, we aimed to investigate the effect of membrane depolarization on the proliferation of SH-SY5Y human neuroblastoma cells. Membrane depolarization induced by 50 mM KCl for 5 min significantly increased SH-SY5Y cell numbers and thymidine incorporation at 24 h after depolarization, and increased the phosphorylation and expression of retinoblastoma protein (RB), the activity of Cdk2 (without changing the activities of Cdk4 and Cdk6), and the expressions of cyclin A and cyclin E. Single and repeated depolarization (once a day for 6 days) had similar effects on RB, Cdks, and cyclins levels and activities. In summary, our results suggest that membrane depolarization may stimulate cellular proliferation by augmenting the expression of cyclin E leading to increases in Cdk2 activity and RB phosphorylation.

Cell Division↗

PubMed2006

NABP1, a novel RORgamma-regulated gene encoding a single-stranded nucleic-acid-binding protein.

RORgamma2 (retinoid-related orphan receptor gamma2) plays a critical role in the regulation of thymopoiesis. Microarray analysis was performed in order to uncover differences in gene expression between thymocytes of wild-type and RORgamma-/- mice. This analysis identified a novel gene encoding a 22 kDa protein, referred to as NABP1 (nucleic-acid-binding protein 1). This subsequently led to the identification of an additional protein, closely related to NABP1, designated NABP2. Both proteins contain an OB (oligonucleotide/oligosaccharide binding) motif at their N-terminus. This motif is highly conserved between the two proteins. NABP1 is highly expressed in the thymus of wild-type mice and is greatly suppressed in RORgamma-/- mice. During thymopoiesis, NABP1 mRNA expression is restricted to CD4+CD8+ thymocytes, an expression pattern similar to that observed for RORgamma2. These observations appear to suggest that NABP1 expression is regulated either directly or indirectly by RORgamma2. Confocal microscopic analysis showed that the NABP1 protein localizes to the nucleus. Analysis of nuclear proteins by size-exclusion chromatography indicated that NABP1 is part of a high molecular-mass protein complex. Since the OB-fold is frequently involved in the recognition of nucleic acids, the interaction of NABP1 with various nucleic acids was examined. Our results demonstrate that NABP1 binds single-stranded nucleic acids, but not double-stranded DNA, suggesting that it functions as a single-stranded nucleic acid binding protein.

Amino Acid Sequence↗

PubMed2006

Regulatory role for Krüppel-like zinc-finger protein Gli-similar 1 (Glis1) in PMA-treated and psoriatic epidermis.

In this study, we analyze the expression and potential function of the Krüppel-like zinc-finger protein Gli-similar protein 1 (Glis1) in normal and inflammatory skin and in the differentiation of epidermal keratinocytes. Glis1 mRNA is not expressed in normal human epidermis, but is significantly induced in psoriatic epidermis and in mouse skin upon treatment with the tumor promoter phorbol-12-myristate-13-acetate (PMA). The expression of Glis1 is restricted to the suprabasal layers. These observations suggest that Glis1 expression is associated with hyperplastic, inflammatory epidermis. Consistent with these findings, Glis1 mRNA is not expressed in undifferentiated or differentiated normal human epidermal keratinocytes (NHEK) in culture, but is dramatically induced after the addition of PMA or interferon gamma. A similar induction of Glis1 mRNA by PMA treatment was observed in the immortalized epidermal keratinocyte cell line NHEK-HPV, whereas PMA did not induce Glis1 in HaCaT cells or in several squamous cell carcinoma cell lines. To obtain insight into its function, Glis1 and a C-terminal deletion mutant Glis1DeltaC were expressed in NHEK-HPV cells and changes in epidermal differentiation and gene expression examined. Microarray analysis revealed that Glis1DeltaC promoted PMA-induced epidermal differentiation, as indicated by increased expression of many differentiation-specific genes. This, in association with its induction in psoriasis, suggests that transcriptional factor Glis1 is involved in the regulation of aberrant differentiation observed in psoriatic epidermis.

Animals↗

PubMed2006

Abdominal pain accompanied by weight loss may increase the diagnostic yield of capsule endoscopy: a Korean multicenter study.

OBJECTIVE: Capsule endoscopy (CE) is approved for the evaluation of obscure gastrointestinal (GI) bleeding and its use has increased in the assessment of patients with various small-bowel disorders. The yield of CE for indications of disorders other than GI bleeding is not yet well described. The aim of the present study was to determine in which subgroup of patients with unexplained abdominal pain, CE would be a helpful evaluation tool. MATERIAL AND METHODS: The results of CE in 110 patients (70 M, 40 F, mean age 50.8+/-14.1 years) with unexplained abdominal pain from 12 tertiary referral centers between September 2002 and September 2004 were retrospectively analyzed. RESULTS: The visualization of the small bowel to the cecum was successfully carried out in 69.1% of the patients. Nineteen out of the 110 cases revealed positive findings that explained the symptoms of the patient (diagnostic yield=17.3%). Diagnosis included small-bowel stricture (5), Crohn's disease (3), small-bowel tumor (2), radiation-induced enteritis (1), NSAID-induced enteropathy (1), ischemic ileitis (1), diffuse lymphangiectasia (1), and significant erosion or ulceration (5). By univariate logistic regression analysis, the positive findings of CE were significantly associated with weight loss (odds ratio (OR), 11.9; 95% CI [2.0, 70.6]), elevated erythrocyte sedimentation rate (ESR) (>20 mm/h) (OR, 11.5; 95% CI (1.9, 69.5)), elevated C-reactive protein (CRP) (>or=0.4 mg/dL) (OR, 5.0; 95% CI (1.6, 15.9)), and hypoalbuminemia (albumin<3 g/dL) (OR, 23.1; 95% CI (2.4, 223.1)). Using a multivariate analysis, weight loss was found to be a significant risk factor for positive findings of CE (OR, 18.6; 95% CI (1.6, 222.4), p=0.02). CONCLUSIONS: The results of this study suggest that CE can be helpful in patients suffering from abdominal pain that cannot be explained by established examinations, if the pain is accompanied by weight loss.

Abdominal Pain↗

PubMed2006

Ceramic failure after total hip arthroplasty with an alumina-on-alumina bearing.

BACKGROUND: The mechanical properties of alumina ceramic, now in its third generation, have been markedly improved through the evolution of design features and manufacturing processes and the introduction of proof-testing. Nonetheless, because of the lack of ductility of alumina ceramic, there is concern regarding the risk of fracture during insertion or in vivo use. The purpose of the present study was to present a multicenter review of primary total hip arthroplasties performed with use of a polyethylene-ceramic composite liner combined with a ceramic femoral head, with particular attention to failure of the ceramic bearing. METHODS: We evaluated 357 primary total hip arthroplasties that had been performed in 319 patients with use of a contemporary alumina-on-alumina bearing design incorporating a polyethylene-ceramic composite liner within a titanium-alloy shell coupled with a 28-mm-diameter ceramic femoral head. The procedures were performed at four participating centers from 1998 to 2001. Ceramic failure without trauma occurred in six hips (1.7%). All of these hips were revised, and the retrieved alumina implants were examined by means of visual inspection and scanning electron microscopy equipped with energy-dispersive x-ray spectrometry. RESULTS: Two femoral heads fractured during the first postoperative year, and four alumina liners fractured after an average of 36.8 months in vivo. All four of the explanted alumina liners revealed evidence of rim contact with the metal neck of the femoral component. Composition analysis confirmed that surface-stain materials were titanium particles transferred from the femoral component. CONCLUSIONS: Despite the theoretical improvement in the fracture toughness of a polyethylene-alumina composite liner, a relatively high rate of catastrophic ceramic bearing surface failure was still observed at the time of short-term follow-up. This finding prompted us to discontinue the use of this type of alumina bearing design.

Adult↗

PubMed2006

Metastasis-associated protein 1 enhances angiogenesis by stabilization of HIF-1alpha.

Metastasis-associated protein 1 (MTA1) is highly upregulated in cancer cells with metastatic potential; however, the molecular mechanism by which MTA1 increases the metastatic potential of cancer cells is unknown. We characterized the functional consequences of MTA1 overexpression in cancer cells with an emphasis on its potential role as a deacetylator of hypoxia-inducible factor-1alpha (HIF-1alpha). MTA1 increased the expression of HIF-1alpha protein, but did not increase the expression of its mRNA. Glutathione S-transferase pull-down and coimmunoprecipitation assays demonstrated direct interaction of MTA1 with HIF-1alpha both in vitro and in vivo. Immunoprecipitation and acetylation assays also showed that MTA1 has deacetylation activity on HIF-1alpha in vivo. Moreover, MTA1 increased the transcriptional activity of HIF-1alpha and enhanced the expression of vascular endothelial growth factor, a target molecule of HIF-1alpha. Conditioned medium collected from MTA1 transfectants also increased angiogenesis in vitro and in vivo, probably through enhanced HIF-1alpha stabilization. These results indicate that MTA1 enhances angiogenesis by stabilization of the HIF-1alpha protein, which is closely related to the increased metastatic potential of cancer cells with high MTA1 expression.

Cell Line, Tumor↗

PubMed2005

Krüppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1).

Glis2 is a member of the Gli-similar (Glis) subfamily of Krüppel-like zinc finger transcription factors. It functions as an activator and repressor of gene transcription. To identify potential co-activators or co-repressors that mediate these actions of Glis2, we performed yeast two-hybrid analysis using Glis2 as bait. C-terminal binding protein 1 (CtBP1) was identified as one of the proteins that interact with Glis2. This interaction was confirmed by mammalian two-hybrid analysis. CtBP1 did not interact with other members of the Glis subfamily suggesting that this interaction is specific for Glis2. Pulldown analysis with GST-CtBP1 demonstrated that CtBP1 physically interacts with Glis2. Analysis of CtBP1 and Glis2 deletion mutants identified several regions important for this interaction. CtBP1 repressed transcriptional activation induced by Glis2(1-171). Repression by Glis2 appears to involve the recruitment of both CtBP1 and histone deacetylase 3 (HDAC3). Confocal microscopic analysis demonstrated that Glis2 localized to nuclear speckles while in most cells CtBP1 was found diffusely in both cytoplasm and nucleus. However, when CtBP1 and Glis2 were co-expressed, CtBP1 was restricted to nuclear speckles and co-localized with Glis2. Our observations suggest that the co-repressor CtBP1 and HDAC3 are part of transcription silencing complex that mediates the transcriptional repression by Glis2.

Alcohol Oxidoreductases↗

PubMed2005

Microtubule affinity-regulating kinase 1 (MARK1) is activated by electroconvulsive shock in the rat hippocampus.

Electroconvulsive shock (ECS) induces phosphorylation and dephosphorylation of many signaling molecules in the rat brain. While studying phosphorylated proteins in the rat brain after ECS, we observed a 100-kDa protein that cross-reacted with anti-phospho-p70 S6 kinase antibody, which was subsequently purified and identified as microtubule affinity-regulating kinase 1 (MARK1). Purified MARK1 was phosphorylated at the Ser and Thr residues. MARK1 activation and subsequent Tau phosphorylation in the hippocampus after ECS was confirmed by an in-gel kinase assay using tau protein as a substrate. MARK1 was maximally activated between 2 and 5 min after ECS, and Tau phosphorylation at Ser262 was also increased at 2 min and lasted to 1 h after ECS. Taken together, we concluded that ECS activated MARK1 and subsequently phosphorylated Tau at Ser262. Both MARK1 activity and Tau phosphorylation were increased in the rat hippocampus after chronic ECS where axonal remodeling was apparent. In order to investigate the physiologic stimuli which are involved in the activation of MARK1, SH-SY 5Y cells were treated with brain-derived neurotrophic factor or 60 mm KCl. Both stimuli were capable of inducing MARK activation.

Amino Acid Sequence↗

PubMed2005

An autocrine or paracrine Fas-mediated counterattack: a potential mechanism for apoptosis of notochordal cells in intact rat nucleus pulposus.

STUDY DESIGN: Immunohistochemistry and in situ nick end-labeling (TUNEL) were performed in rat lumbar intervertebral discs. OBJECTIVES: To demonstrate the mechanism of notochordal cell death in the nucleus pulposus (NP). SUMMARY OF BACKGROUND DATA: With age, notochordal cells gradually disappear in the NP. We hypothesized that this phenomenon might be related to Fas-mediated apoptosis. MATERIALS AND METHODS: Expressions of Fas; Fas ligand (FasL); caspase 3, 8, 9, 10; Ki-67 protein; and TUNEL were examined in 4-week-, 6-month- and 12-month-old rat NPs. Apoptosis (TUNEL-positive) and proliferation potential (Ki-67-positive) indexes of notochordal cells were calculated and compared among age groups. RESULTS: Notochordal cells constitutively expressed both Fas and FasL. Among their downstream initiator (caspase 8, 9, and 10) and executioner (caspase 3) caspases tested, caspase 9 and 3 were expressed. Proliferation potential of the notochordal cells was the highest at 4 weeks (1.96 +/- 1.3%) and decreased to a significantly lower level at 6 (0.81 +/- 0.68%) and 12 months (0.8 +/- 0.37%; P = 0.03 and 0.01, respectively). In contrast, apoptosis of the notochordal cells was the lowest at 4 weeks (3.52 +/- 1.07%) and increased to a significantly higher level at 6 (19.38 +/- 10.99%) and 12 months (21.51 +/- 16.99%; P < 0.001 in both comparisons). CONCLUSIONS: Fas-mediated mitochondrial caspase 9 pathway is constitutively present in the rat notochordal cells. The constitutive expression of Fas, FasL and its downstream caspases, as well as the homogeneity ofnotochordal cell population suggests an autocrine or paracrine Fas-mediated counterattack to be a potential mechanism for apoptosis of rat notochordal cells. A regulated negative balance of notochordal cell proliferation against apoptosis is likely to involve the disappearance of notochordal cells in the rat NP. This information on the mechanism for apoptosis of notochordal cells could be important in the investigation of intervertebral disc development as well as aging and perhaps degeneration.

Aging↗

PubMed2005

Fatty marrow conversion of the proximal femoral metaphysis in transient bone marrow edema syndrome.

INTRODUCTION: In the proximal femoral metaphysis, hematopoietic marrow is predominant during the adult stage of life. The conversion of hematopoietic marrow to fatty marrow in the proximal femoral metaphysis has been suggested as an etiologic factor of ischemia in the pathogenesis of femoral head osteonecrosis. To determine whether the chronology of fatty marrow conversion of the proximal femoral metaphysis is related to transient bone marrow edema syndrome of the hip, a case control study was conducted on 10 patients with the disease. MATERIALS AND METHODS: There were 8 men and 2 women with a mean age of 33 years (range 19-45 years). The 10 patients were matched with 20 controls for gender and age (5-year range). T1-weighted MRI scans of their hips were reviewed. Marrow of the greater trochanter becomes fatty before puberty, and thus, the greater trochanter can be used as a built-in control. The signal intensity of the proximal femoral metaphysis was compared to that of the greater trochanter. RESULTS: In all patients, the signal intensity of the proximal femoral metaphysis was isointense (fatty marrow) relative to that of the greater trochanter. In control subjects, the signal intensity was isointense in 8 (40%) and hypointense (hematopoietic marrow) in 12 (60%) (p < 0.05). CONCLUSION: The current study shows that the proximal femoral metaphysis is predominantly fatty in transient bone marrow edema syndrome. The conversion of hematopoietic to fatty marrow is known to correlate with decreases in intramedullary blood flow. Thus, the current study suggests that an ischemia of the proximal femur secondary to fatty marrow conversion of the proximal femoral metaphysis might be a cause of transient bone marrow edema syndrome of the hip.

Adult↗

PubMed2005

Membrane depolarization induces the undulating phosphorylation/dephosphorylation of glycogen synthase kinase 3beta, and this dephosphorylation involves protein phosphatases 2A and 2B in SH-SY5Y human neuroblastoma cells.

Changes in plasma membrane electrical potential evoke signals that regulate the expressions of various genes in the nervous system. However, the role of glycogen synthase kinase 3beta (GSK-3beta) in this process has not been elucidated. Thus, this study was performed to examine whether membrane depolarization can regulate the phosphorylation of GSK-3beta and to identify the molecular mechanisms involved in this regulation. The depolarization by treating with 100 mm KCl for 5 min resulted in the undulating phosphorylation of GSK-3beta at Ser-9 in SH-SY5Y human neuroblastoma cells, in H19 -7/IGF-IR rat embryonic hippocampal cells, and in PC12 rat pheochromocytoma cells, but not in A172 human glioblastoma cells. Cellular beta-catenin contents showed a temporal pattern similar to that of the Ser-9 phosphorylation of GSK-3beta. Treatment with wortmannin or calphostin C or the expression of dominant negative Akt inhibited phosphorylation of GSK-3beta at Ser-9 following the KCl-induced depolarization of SH-SY5Y cells. Moreover, pretreatment with okadaic acid or cyclosporin A blocked the dephosphorylation of GSK-3beta at Ser-9 at 0, 15, and 30 min after KCl-induced depolarization, and the activity of protein phosphatases (PP) 2A and 2B increased at these times. Treatment with nifedipine or calcium-free medium inhibited GSK-3beta dephosphorylation following membrane depolarization, and the amounts of co-immunoprecipitated GSK-3beta and PP2A changed in parallel with GSK-3beta dephosphorylation. Our study demonstrated that KCl-induced depolarization caused undulating GSK-3beta phosphorylation/dephosphorylation, which was regulated for the most part by phosphatidylinositol 3-kinase and Akt (phosphorylation) and PP2A and PP2B (dephosphorylation), respectively.

Androstadienes↗

PubMed2005

Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) as a subjective measure of drug-induced parkinsonism and akathisia.

The Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) was examined for its usefulness as a subjective measure of drug-induced parkinsonism and akathisia. Eighty-three subjects were assessed using the LUNSERS, the Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), before and after a 6-week treatment with olanzapine. Significant correlations were found between the changes in scores of parkinsonism items of LUNSERS and SAS. The changes in scores of akathisia item (restlessness), extrapyramidal side effects (EPS) subscale and psychic side-effects subscale of LUNSERS were significantly correlated with those of the BARS. 'Shakiness', one item of the EPS subscale of LUNSERS, correctly classified between parkinsonism and non-parkinsonism groups with 81.0% accuracy. A combination of four items included in EPS and psychic side-effect subscales of LUNSERS identified akathisia and non-akathisia groups with 76.2% accuracy. These results suggest that the EPS and psychic side-effect subscales of LUNSERS may be useful in screening for drug-induced parkinsonism and akathisia.

Adult↗

PubMed2005

Tryptophan hydroxylase polymorphism is associated with age of onset of alcoholism related behaviors.

The purpose of this study was to explore the association of a tryptophan hydroxylase gene polymorphism (TPH1 A218C) with the age of alcoholism onset in a Korean population. The genotype and allele frequencies of TPH1 were investigated in 182 male hospitalized patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for alcohol dependence. Alcoholics with the TPH1 AA or AC genotypes had an earlier age of disease onset (median age of onset, 26.5 years) than those with the CC genotype (median age of onset, 30 years; p=.002). Age of onset has been used in classifying alcoholics. The TPH1 polymorphism may explain, in part, the biological basis for these typologies.

Adult↗

PubMed2004

TIP27: a novel repressor of the nuclear orphan receptor TAK1/TR4.

The nuclear orphan receptor TAK1/TR4 functions as a positive as well as a negative regulator of transcription; however, little is known about the factors regulating or mediating its activity. Yeast two-hybrid analysis using the ligand-binding domain (LBD) of TAK1 as bait identified a novel TAK1-interacting protein, referred to as TIP27, which functions as a repressor of TAK1-mediated transactivation. TIP27 is a 27 kDa protein containing two zinc finger motifs. Mammalian two-hybrid analysis showed that TIP27 interacts specifically with TAK1 and not with several other nuclear receptors tested. The region between Asp39 and Lys79 of TIP27, referred to as TAK1-interaction domain (TID), is critical for its interaction with TAK1 while the TAK1-LBD from helix 3 until the C-terminus is required for the optimal interaction with TIP27. Pull-down assays demonstrated that the TIP27 physically interacts with TAK1 and supported the critical importance of the TID. Confocal microscopy showed that in the nucleus, TIP27 and TAK1 co-localize. TIP27 acts as a strong repressor of DR1-dependent transcriptional activation by TAK1. This repression does not involve the inhibition of TAK1 homodimerization or DR1 binding but may be due to an effect on co-activator recruitment by TAK1. Our results indicate that TIP27 functions as a TAK1-selective repressor.

Amino Acid Sequence↗

PubMed2003

GLIS3, a novel member of the GLIS subfamily of Krüppel-like zinc finger proteins with repressor and activation functions.

In this study, we describe the identification and characterization of a novel transcription factor GLI-similar 3 (GLIS3). GLIS3 is an 83.8 kDa nuclear protein containing five C2H2-type Krüppel-like zinc finger motifs that exhibit 93% identity with those of GLIS1, however, little homology exists outside their zinc finger domains. GLIS3 can function as a repressor and activator of transcription. Deletion mutant analysis determined that the N- and C-termini are required for optimal transcriptional activity. GLIS3 binds to the GLI-RE consensus sequence and is able to enhance GLI-RE-dependent transcription. GLIS3(DeltaC496), a dominant-negative mutant, inhibits transcriptional activation by GLIS3 and GLI1. Whole mount in situ hybridization on mouse embryos from stage E6.5 through E14.5 demonstrated that GLIS3 is expressed in specific regions in developing kidney and testis and in a highly dynamic pattern during neurulation. From E11.5 through E12.5 GLIS3 was strongly expressed in the interdigital regions, which are fated to undergo apoptosis. The temporal and spatial pattern of GLIS3 expression observed during embryonic development suggests that it may play a critical role in the regulation of a variety of cellular processes during development. Both the repressor and activation functions of GLIS3 may be involved in this control.

Amino Acid Sequence↗

PubMed2003

Tsp57: a novel gene induced during a specific stage of spermatogenesis.

Recently, we described the identification of a novel protein, nuclear receptor-associated protein 80 (RAP80), which is highly expressed in spermatocytes and appears to have a role in regulating gene expression. To identify proteins interacting with this protein, we performed yeast two-hybrid screening using full-length RAP80 as bait. This screen identified one in-frame clone encoding a novel testis-specific protein (Tsp), referred to as Tsp57. Tsp57 encodes a basic protein with a mass of 56.8 kDa. The amino acid sequence of Tsp57 is highly conserved (87%) between mouse and human. The mouse and human Tsp57 genes map to chromosomes 9A1 and 11q21, respectively. Northern blot analysis showed that the expression of Tsp57 mRNA was highly restricted to the testis and temporally regulated during testicular development. Tsp57 mRNA was greatly induced between Day 21 and Day 25 of postnatal testicular development. In situ hybridization analysis demonstrated that the hybridization signal for Tsp57 mRNA was strongest in sections of seminiferous tubules at stages VI-VIII of spermatogenesis, consistent with the conclusion that Tsp57 is most highly expressed in round spermatids. Study of Tsp57 expression in several purified subpopulations of spermatogenic cells confirmed maximum levels of expression in round spermatids. Consistently, Tsp57 expression was absent in testes from vitamin A-deficient mice, which do not have any round spermatids, and was reduced in RARalpha null mice, which have lowered numbers of round spermatids in their testes. These results indicate the possibility that Tsp57 protein plays a role in the postmeiotic phase of germ cell differentiation. Tsp57 contains two putative nuclear localization signals: NLS1 and NLS2. Examination of the cellular localization showed that the green fluorescent protein-Tsp57 fusion protein localized to both cytoplasm and nucleus. After deletion of NLS1 but not NLS2, Tsp57 localized solely to the cytoplasm, indicating a role for NLS1 in the nuclear localization of Tsp57. The localization suggests a nuclear function for Tsp57. Pull-down analysis demonstrated that Tsp57 and RAP80 form a complex in intact cells.

Amino Acid Sequence↗

PubMed2003

Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson's disease model.

Parkinson's disease (PD) is a chronic neurodegenerative disorder, and it has been suggested that treatments promoting survival and functional recovery of affected dopaminergic neurons could have a significant and long-term therapeutic value. In the present study, we investigated the neuroprotective effects of acupuncture on the nigrostriatal system in rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA, 4 microg/microl, intrastriatal injection) using tyrosine hydroxylase (TH) and receptor for brain-derived neurotrophic factor, trkB, immunohistochemistries. Two weeks after the lesions were made, rats presented with asymmetry in rotational behavior (118.3 +/- 17.5 turns/h) following injection with apomorphine, a dopamine receptor agonist (0.5 mg/kg, sc). In contrast, acupunctural treatment at acupoints GB34 and LI3 was shown to significantly reduce this motor deficit (14.6 +/- 13.4 turns/h). Analysis via TH immunohistochemistry revealed a substantial loss of cell bodies in the substantia nigra (SN) (45.7% loss) and their terminals in the dorsolateral striatum ipsilateral to the 6-OHDA-induced lesion. However, acupunctural treatment resulted in the enhanced survival of dopaminergic neurons in the SN (21.4% loss) and their terminals in the dorsolateral striatum. Acupuncture also increased the expression of trkB significantly (35.6% increase) in the ipsilateral SN. In conclusion, we observed that only acupuncturing without the use of any drug has the neuroprotective effects against neuronal death in the rat PD model and these protective properties of acupuncture could be mediated by trkB.

Acupuncture Therapy↗