PubMed Health⌕ Search

Biomedical subjects

J Oikarinen

Publications and source records attributed to J Oikarinen.

At least 19 recordsLinked to original sources
PubMed1997

Nucleotide and calcium-induced conformational changes in histone H1.

The principal constituents of chromatin, histone H1 (H1) and the nucleosome have essential roles in regulation of eukaryotic gene expression. However, mechanisms for the H1-dependent inactivation and for the ATP-dependent chromatin remodeling upon activation are largely unelucidated. Using circular dichroism (CD) analysis we show that ATP and other nucleotides and Ca2+ induce structural changes in H1. ATP and Ca2+ also induce changes when H1 is interacting with DNA, and the changes in H1 are accompanied by alterations in its DNA interaction. These results suggest that nucleotide and Ca2+ binding may be important for H1-mediated chromatin changes.

Adenine Nucleotides↗
PubMed1997

Steroid-involved transcriptional regulation of human genes encoding prostatic acid phosphatase, prostate-specific antigen, and prostate-specific glandular kallikrein.

We have compared the steroid regulation of human genes encoding prostatic acid phosphatase (hPAP), prostate-specific antigen (hPSA), and prostate-specific glandular kallikrein (hK2) at the level of transcription. Reporter constructs of hPAP promoter covering the region -734/+467 were functional in both prostatic (LNCaP and PC-3) and nonprostatic (CV-1) cell lines in transient transfections. hPAP -231/+50 with eight identified transcription factor-binding sites showed the highest, and hPAP -734/+467 showed the lowest transcriptional activity in CV-1 cells. The hPAP promoter could not be induced with androgen, glucocorticoid, or progesterone, contrary to the hPSA (-620/+40) and hK2 (-493/+27) promoters in PC-3 cells cotransfected with the respective steroid receptor expression vector. Therefore, steroids cannot directly regulate hPAP gene expression via receptor binding to steroid response elements at -178 and +336, which have been shown to have androgen receptor-binding ability in vitro. Glucocorticoid was the most powerful activator of the hPSA construct at 10-nM steroid concentrations. On the contrary, glucocorticoid stimulation of the transcriptional activity of the hK2 construct was the weakest among the tested steroids. The results indicate that the steroid response elements in the proximal promoters of hPSA and hK2 genes are not androgen specific, offering the molecular basis for the expression of these genes outside the prostate in tissues containing steroid receptors.

Acid Phosphatase↗
PubMed1997

Computed tomography data based rapid prototyping model of the temporal bone before cochlear implant surgery.

Rapid prototyping (RP) technique allows automatic fabrication of 3D model parts. This method was applied to make a temporal bone model before cochlear implant surgery. A helical CT scan is used to acquire high resolution data from the middle and the inner ear of the patient. From the scanning data bone structures and soft tissues can be separated because their different grayscale pixel values. By using a guided image processing tool the desired parts of the anatomy can be extracted and 3D data created. The segmented data are processed to the form suitable for creating a high accuracy RP model. The RP model is made in the stereolithography (SLA) process by means of a computer guided HeCd laser beam inducing polymerisation of acrylic solution as it passes layer by layer over the surface of the polymer solution. In this prototype model the anatomy of the temporal bone can be clearly visualised, including, e.g., mastoid cells, tympanic cavity, bony canal of facial nerve, and round and oval windows. The inner ear spaces including vestibule, semicircular canals and cochlear turn are also shaped. The transparent acrylic material allows bonelike mechanical handling. The RP model can be dissected and used in individual surgical planning and simulation prior to cochlear implantation.

Cochlear Implants↗
PubMed1995

The ATP/ADP binding domains of actin are conserved in nucleosome complexed with histone H1 and high mobility group-17 protein.

Chromatin has been proposed to share a common evolutionary origin and analogous mechanisms of action with various structures of cytoskeleton such as actin filaments. ATP has been shown to facilitate chromatin remodelling, but the exact site of its interaction with chromatin has not been elucidated. The facts, that ATP binds specifically to actin and promotes its polymerization, led us to characterize the possible domains involved in ATP binding in nucleosome. Comparison of the sequences of actin and the protein components of nucleosome suggests that H2A may contain an adenosine binding site similar to the adenosine motif of actin, H1 and/or H2B phosphate/Ca2+ binding sites corresponding to the phosphate 1 motif of actin, HMG17 a phosphate/Ca2+ binding site corresponding to the phosphate 2 motif of actin. The ability to bind ATP may be involved in the organization of chromatin into inactive solenoid-like structures in vivo.

Actins↗
PubMed1995

Coordination of transcription of the human 17 beta-hydroxysteroid dehydrogenase type 1 gene (EDH17B2) by a cell-specific enhancer and a silencer: identification of a retinoic acid response element.

Human 17 beta-hydroxysteroid dehydrogenase type 1 (17HSD type 1) catalyzes primarily the reductive reaction of estrone to the biologically more active form, estradiol. The enzyme is highly expressed in the human placenta and the ovary and, in addition, in certain estrogen target cells, such as breast epithelial cells. To elucidate the transcriptional control of the EDH17B2 gene, the gene encoding 17HSD type 1, we fused a series of 5'-deletion mutants of the EDH17B2 gene into chloramphenicol acetyl transferase reporter gene vectors. An enhancer region was identified within the bases -661 to -392 and it increased, in both orientations, thymidine kinase promoter activity more than 200-fold in JEG-3 choriocarcinoma cells. This enhancer region was also functional in another choriocarcinoma cell line, JAR, although to a lesser extent. In BT-20 and T-47D breast cancer cells the enhancer region increased thymidine kinase promoter activity to some degree but not as efficiently as expected on the basis of endogenous enzyme expression. No such enhancer activity was observed in 17HSD type 1 nonexpressing cell lines. The retinoic acid responsive element, which was located between bases -503 and -487 in the EDH17B2 enhancer, bound retinoid acid receptor alpha retinoid X receptor alpha complex and transmitted retinoic acid induction on transcription in JEG-3 and T-47D cells. Finally, a silencer, functional in all the cell lines tested, was localized in the region from -392 to -78. Deletion of the region lad to a 4-fold increase in reporter gene expression. Altogether, our findings suggest that transcriptional control of the EDH17B2 gene is coordinated by the cell-specific enhancer and the silencer.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

The 90 kDa heat shock protein (hsp90) induces the condensation of the chromatin structure.

The 90 kDa heat shock protein (hsp90) is a member of the "chaperone-complex" of steroid receptors believed to be partially or transiently localized in the cell nucleus. Demonstrating that hsp90 has an ATP binding site and autophosphorylating activity we have observed that histones, especially histone H1, are able to modulate the autophosphorylation of hsp90 [Csermely, P. and Kahn, C.R. (1991) J. Biol. Chem. 266, 4943-4950]. Our present data suggest a direct interaction of hsp90 with histones, showing that hsp90 is able to bind histone-agarose and enhances the binding of histones to DNA. Circular dichroism spectra of rat liver chromatin indicate that hsp90 induces a tighter, condensed state of the chromatin structure which is resistant against disruption by high salt treatment. Interactions of hsp90 with the chromatin may be important in regulating the transcriptional activity of steroid receptors and other transcription factors.

Animals↗
PubMed1994

Nucleotide recognition by histone H1 involves specific protein structures.

We have reported previously that histone H1 is capable of binding nucleotides such as ATP, GTP, ADP, and GDP in a specific manner. It is demonstrated here using labeling with the uv-crosslinkable ATP analog 8-azido-[alpha-32P]ATP that this ability is a unique characteristic of H1 among the histone proteins. Phosphate analogs such as AlF-4 efficiently counteract the labeling of H1, while they do not compete for labeling of histones H2A, H2B, H3, and H4. Consistent with the assumption that this labeling is due to specific binding, nucleotides competed for the labeling of H1 in a manner similar to labeling of the catalytic subunit of cAMP-dependent protein kinase, casein kinase-II, and heat shock protein-90, all of which are ATP/GTP-binding proteins. The site of nucleotide interaction was subsequently located in a Gly-rich region of H1 which displays homology with the protein kinases, using either radioactive labeling with nucleotide analogs and endoproteinase Glu-C digestion or synthetic peptides corresponding to the putative binding site. The results imply that specific protein structures are involved in nucleotide binding to H1 and that the ability of H1 to bind nucleotides may provide a mechanism for the regulation of eukaryotic gene expression.

Acetyl Coenzyme A↗
PubMed1993

Interaction of transcription factor Sp1 with the promoter of the gene for the multifunctional protein disulphide isomerase polypeptide.

Protein disulphide isomerase (PDI) is a unique polypeptide which resides in the lumen of the endoplasmic reticulum and also functions as the beta-subunit of prolyl 4-hydroxylase, as a cellular thyroid hormone-binding protein, as the smaller subunit of the microsomal triacylglycerol transfer protein complex, as a dehydroascorbate reductase and as a protein that binds various peptides in a specific manner. We have recently demonstrated that the promoter of the PDI gene contains six CCAAT boxes and other elements which are needed for efficient transcription. We now demonstrate that purified human recombinant transcription factor Sp1 interacts with two perfect GGGCGG sequences and three other GC-rich elements of the PDI promoter. Sp1 also appears to participate in the regulation of PDI gene expression, since overexpression of Sp1 stimulated PDI promoter activity in HeLa cells and mutations introduced into each of these Sp1-binding sites separately reduced the promoter strength, although even the largest decrease was only about 50%. These results support our view that expression of the gene for this polypeptide with multiple functions is secured by several regulatory elements, some of which are functionally redundant.

Base Sequence↗
PubMed1993

Specific non-enzymatic glycation of the rat histone H1 nucleotide binding site in vitro in the presence of AlF4-. A putative mechanism for impaired chromatin function.

We show here that an aluminium derivative, AlF4-, stimulates glycation of histone H1 selectively in the proximity of its nucleotide-binding site. This adduct formation interferes with nucleoside triphosphate hydrolysis by H1 and with nucleotide modulation of H1 DNA binding. The present mode of aluminium action may in part be responsible for its effects on the chromatin structure and expression of tissue-specific genes, and may constitute a mechanism in the pathogenesis of aluminium-induced encephalopathy and in that of Alzheimer's disease, for example.

Aluminum↗
PubMed1993

Neuronavigator-guided cerebral biopsy.

Neuronavigators are new dynamic interactive instruments that use on-line computers to orient imaging data to the surgical field and guide the neurosurgeon to his target. We have been working since 1987 on a neuronavigator that serves not only as a precise pointer, but also as a dynamic arm that can be used to hold instruments, such as biopsy guides. The neuronavigator arm consists of six joints with optical encoders and is attached to the Mayfield headholder. The arm is connected to a workstation running customized 3D image graphics software. Special instruments and surgical technique have been developed. Here, we report on early clinical experience with ten biopsy procedures: 4 low-grade and 3 high-grade astrocytomas, one craniopharyngioma and one chronic intracerebral haematoma and intracerebral cyst, both of the latter with surrounding tumour suspect tissue. In all glioma cases serial biopsies were taken from optimal sites under ultrasound imaging control. Eight cases showed representative tumour tissue, while in two cases neoplasia was ruled out. The neuronavigator proved to be versatile, allowing comprehensive imaging data to be adapted to the surgical field.

Astrocytoma↗
PubMed1993

Ultrasound-controlled neuronavigator-guided brain surgery.

The development of a unique neurosurgical navigator is described and a preliminary series of seven cases of intracerebral lesions approached with the assistance of this neuronavigation system under ultrasound control is presented. The clinical series included five low-grade astrocytomas, one chronic intracerebral hematoma, and one porencephalic cyst. Management procedures included biopsy in all cases, drainage of the hematoma, and endoscopy and fenestration for the cyst. The features of the neuronavigation system are interactive reconstructions of preoperative computerized tomography and magnetic resonance imaging data, corresponding intraoperative ultrasound images, versatility of the interchangeable end-effector instruments, graphic presentation of instruments on the reconstructed images, and voice control of the system. The principle of a common axis in the reconstructed images served to align the navigational pointer, biopsy guide, endoscope guide, ultrasound transducer, and surgical microscope to the brain anatomy. Intraoperative ultrasound imaging helped to verify the accuracy of the neuronavigator and check the results of the procedures. The arm of the neuronavigation system served as a holder for instruments, such as the biopsy guide, endoscope guide, and ultrasound transducer, in addition to functioning as a navigational pointer. Also, the surgical microscope was aligned with the neuronavigator for inspection and biopsy of the hematoma capsule to rule out tumor etiology. Voice control freed the neurosurgeon from manual exercises during start-up and calibration of the system.

Adult↗
PubMed1992

DNA binding of histone H1 is modulated by nucleotides.

Histone H1 acts as a general repressor of transcription in eukaryotes by organizing nucleosomes into inaccessible condensed forms of chromatin. The capability of H1 to bind to DNA with some sequence specificity is likely to be critical in the control of these processes. We show here that ATP and several other nucleotides, including non-hydrolyzable derivatives, can inhibit DNA binding of H1. The results also show that ATP differentially affects binding of H1 to DNA in a fashion enhancing nucleotide sequence specificity of the binding. The study suggests a novel mechanism of modulation of H1 activity that has important implications for the role of H1 as a transcriptional regulator.

Amino Acid Sequence↗
PubMed1992

Promoter of the gene for the multifunctional protein disulfide isomerase polypeptide. Functional significance of the six CCAAT boxes and other promoter elements.

Protein disulfide isomerase (PDI) is a highly unusual multifunctional polypeptide that is identical to the beta-subunit of prolyl 4-hydroxylase, a cellular thyroid hormone-binding protein and a subunit of the microsomal triglyceride transfer protein complex, and very similar to a polypeptide functioning in vitro as a glycosylation site binding protein of oligosaccharyl transferase. The human PDI gene possesses several putative transcriptional control elements, including the highly unusual presence of six CCAAT boxes between -108 and -378 of the 5'-flanking region. We report here on a promoter analysis of this gene. Eleven PDI promoter elements recognized by DNA-binding proteins present in HeLa cell and HT-1080 cell nuclear extracts were identified by DNase I footprinting analysis within the first 630 nucleotides of the 5'-flanking region. Interestingly, these included all six CCAAT elements. Functional 5' deletion analysis suggested that only two or three of the CCAAT elements may contribute significantly to the promoter activity in HeLa cells. Mutations introduced into each of the CCAAT boxes separately indicated, however, that all six appear to contribute to the promoter strength, the largest decreases (approximately 50%) being seen with mutations in the second or fifth CCAAT box. These data thus suggested that efficient expression of the multifunctional PDI polypeptide is secured by multiple CCAAT elements, some of which appear to be functionally redundant. The 5' deletion analysis further suggested that a region between -623 and -518 may contain additional positively and negatively acting elements.

Base Sequence↗
PubMed1992

Nucleoside triphosphate binding and hydrolysis by histone H1.

We present here further evidence supporting that histone H1 contains a nucleotide binding site interacting e.g. with ADP, ATP, GDP and GTP. The finding is in accordance with the previous observation that nucleotides modulate recognition of DNA by H1. Most interestingly, H1 appears to be capable of hydrolyzing NTPs and incorporating phosphate to exogenous proteins. The mode of nucleotide action on H1 may be considered highly analogous to that of GTPases. Nuclear receptors may thus act through mechanisms similar to those for receptors on the plasma membrane.

Acetyl Coenzyme A↗
PubMed1991

Histone H1 and the regulation of transcription by nuclear receptors.

Histone H1 is a eukaryotic repressor which recognizes specific DNA structures, and nucleotides regulate its interaction with DNA. Since their mode of action may be considered similar to that observed in the case of plasma membrane GTPases, H1 may be regarded as an ATP/GTPase involved in the action of nuclear receptors. A hypothesis is put forward here to suggest that transcriptional activators CTF/NF-I and AP-1 (fos/jun), for example, are effectors for H1. H1 and CTF/NF-I may be members of a stimulatory regulatory cascade for nuclear receptor action that ends with selective activation of chromatin through histone modification and the disruption or a more subtle structural change of a specific nucleosome, while an opposite effect may be obtained through modification of fos/jun by H1.

Animals↗
PubMed1991

Interference of AlF4- with nucleotide and DNA binding of rat histone H1 in vitro. Implications for the pathogenesis of Alzheimer's disease.

We demonstrate here that the H2PO4- analogue AlF4- binds to the nucleotide-binding site of rat liver histone H1 in vitro, and interferes with nucleotide recognition and H1 DNA binding. AlF4- may thus compromise the genetically determined pattern of protein synthesis through binding to H1, the general repressor. The present findings are of interest as a number of studies have implicated aluminium as a factor in the pathogenesis of Alzheimer's disease.

Aluminum↗
PubMed1991

Homologous structures of nuclear and GTPase-linked plasma membrane receptors suggest analogous mechanisms of action.

The molecular structures of nuclear and GTPase-linked plasma membrane receptors are compared here in the light of a recent finding suggesting that histone H1 may be an ATP/GTPase involved in transduction of the action of nuclear receptors. Considerable homology and conservation of the regions responsible for the interaction of the plasma membrane receptors with GTPases was observed in the nuclear receptors, thus suggesting analogous mechanisms of action and a common evolutionary origin for the two receptor families.

Amino Acid Sequence↗