Up-Regulation of the Gene Encoding Protein Kinase A Type Iα Regulatory Subunit in Nodular Hyperplasia of Parathyroid Glands in Patients with Chronic Renal Failure
Context: Hyperplasia of parathyroid glands in patients with chronic renal failure is classified into diffuse (DH) and nodular (NH) types, and NH is often refractory to routine medical therapy. Objective: Although it is considered that the parenchymal cells initially proliferate diffusely and then so...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2006-02, Vol.91 (2), p.563-568 |
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| container_title | The journal of clinical endocrinology and metabolism |
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| creator | Hibi, Yatsuka Kambe, Fukushi Tominaga, Yoshihiro Mizuno, Yutaka Kobayashi, Hironobu Iwase, Katsumi Imai, Tsuneo Seo, Hisao |
| description | Context: Hyperplasia of parathyroid glands in patients with chronic renal failure is classified into diffuse (DH) and nodular (NH) types, and NH is often refractory to routine medical therapy.
Objective: Although it is considered that the parenchymal cells initially proliferate diffusely and then some of them are transformed to form nodules consisting of monoclonal cells, the underlying molecular mechanism for such a transformation is not fully understood. In this study we tried to identify the genes that are up-regulated in NH.
Design and Setting: The cDNA population prepared from DH was subtracted from that prepared from NH by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned and sequenced. To confirm the up-regulation of the identified genes, a total of 35 parathyroid glands (18 DH, 16 NH, and one mixed) obtained from 21 patients were analyzed.
Results: One of the nuclear genes identified was the PRKAR1A gene, which encodes type Iα regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA). Immunohistochemical analysis demonstrated that RIα was abundantly expressed in the nodular region, whereas the adjacent diffuse region displayed relatively low expression. Northern and Western blot analyses demonstrated up-regulation of RIα expression in most NH tested. Determination of PKA activities revealed that free PKA activities measured in the absence of cAMP in the assay were inversely correlated with RIα expression, indicating the functional significance of RIα up-regulation.
Conclusions: These results suggest that the aberrant expression of RIα is involved in the diffuse to nodular transformation of hyperplasia of parathyroid glands by impairing cAMP/PKA signal transduction. |
| doi_str_mv | 10.1210/jc.2005-2155 |
| format | Article |
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Objective: Although it is considered that the parenchymal cells initially proliferate diffusely and then some of them are transformed to form nodules consisting of monoclonal cells, the underlying molecular mechanism for such a transformation is not fully understood. In this study we tried to identify the genes that are up-regulated in NH.
Design and Setting: The cDNA population prepared from DH was subtracted from that prepared from NH by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned and sequenced. To confirm the up-regulation of the identified genes, a total of 35 parathyroid glands (18 DH, 16 NH, and one mixed) obtained from 21 patients were analyzed.
Results: One of the nuclear genes identified was the PRKAR1A gene, which encodes type Iα regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA). Immunohistochemical analysis demonstrated that RIα was abundantly expressed in the nodular region, whereas the adjacent diffuse region displayed relatively low expression. Northern and Western blot analyses demonstrated up-regulation of RIα expression in most NH tested. Determination of PKA activities revealed that free PKA activities measured in the absence of cAMP in the assay were inversely correlated with RIα expression, indicating the functional significance of RIα up-regulation.
Conclusions: These results suggest that the aberrant expression of RIα is involved in the diffuse to nodular transformation of hyperplasia of parathyroid glands by impairing cAMP/PKA signal transduction.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jc.2005-2155</identifier><identifier>PMID: 16303839</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Biological and medical sciences ; Blotting, Northern ; Blotting, Western ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ; Cyclic AMP-Dependent Protein Kinases ; Endocrinopathies ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Enzymologic ; Humans ; Hyperparathyroidism, Secondary - complications ; Hyperparathyroidism, Secondary - enzymology ; Hyperparathyroidism, Secondary - genetics ; Hyperparathyroidism, Secondary - pathology ; Immunohistochemistry ; Kidney Failure, Chronic - complications ; Kidney Failure, Chronic - enzymology ; Kidney Failure, Chronic - pathology ; Medical sciences ; Nucleic Acid Hybridization ; Parathyroid Glands - enzymology ; Proteins - genetics ; Proteins - metabolism ; RNA - chemistry ; RNA - genetics ; Up-Regulation ; Vertebrates: endocrinology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2006-02, Vol.91 (2), p.563-568</ispartof><rights>Copyright © 2006 by The Endocrine Society</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4777-bdad8e8e14809c30ca2698aca3bc332dbe2ccf2b53001f062d76869e4db48e593</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17489985$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16303839$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hibi, Yatsuka</creatorcontrib><creatorcontrib>Kambe, Fukushi</creatorcontrib><creatorcontrib>Tominaga, Yoshihiro</creatorcontrib><creatorcontrib>Mizuno, Yutaka</creatorcontrib><creatorcontrib>Kobayashi, Hironobu</creatorcontrib><creatorcontrib>Iwase, Katsumi</creatorcontrib><creatorcontrib>Imai, Tsuneo</creatorcontrib><creatorcontrib>Seo, Hisao</creatorcontrib><title>Up-Regulation of the Gene Encoding Protein Kinase A Type Iα Regulatory Subunit in Nodular Hyperplasia of Parathyroid Glands in Patients with Chronic Renal Failure</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Context: Hyperplasia of parathyroid glands in patients with chronic renal failure is classified into diffuse (DH) and nodular (NH) types, and NH is often refractory to routine medical therapy.
Objective: Although it is considered that the parenchymal cells initially proliferate diffusely and then some of them are transformed to form nodules consisting of monoclonal cells, the underlying molecular mechanism for such a transformation is not fully understood. In this study we tried to identify the genes that are up-regulated in NH.
Design and Setting: The cDNA population prepared from DH was subtracted from that prepared from NH by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned and sequenced. To confirm the up-regulation of the identified genes, a total of 35 parathyroid glands (18 DH, 16 NH, and one mixed) obtained from 21 patients were analyzed.
Results: One of the nuclear genes identified was the PRKAR1A gene, which encodes type Iα regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA). Immunohistochemical analysis demonstrated that RIα was abundantly expressed in the nodular region, whereas the adjacent diffuse region displayed relatively low expression. Northern and Western blot analyses demonstrated up-regulation of RIα expression in most NH tested. Determination of PKA activities revealed that free PKA activities measured in the absence of cAMP in the assay were inversely correlated with RIα expression, indicating the functional significance of RIα up-regulation.
Conclusions: These results suggest that the aberrant expression of RIα is involved in the diffuse to nodular transformation of hyperplasia of parathyroid glands by impairing cAMP/PKA signal transduction.</description><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Blotting, Western</subject><subject>Cyclic AMP-Dependent Protein Kinase RIalpha Subunit</subject><subject>Cyclic AMP-Dependent Protein Kinases</subject><subject>Endocrinopathies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>Humans</subject><subject>Hyperparathyroidism, Secondary - complications</subject><subject>Hyperparathyroidism, Secondary - enzymology</subject><subject>Hyperparathyroidism, Secondary - genetics</subject><subject>Hyperparathyroidism, Secondary - pathology</subject><subject>Immunohistochemistry</subject><subject>Kidney Failure, Chronic - complications</subject><subject>Kidney Failure, Chronic - enzymology</subject><subject>Kidney Failure, Chronic - pathology</subject><subject>Medical sciences</subject><subject>Nucleic Acid Hybridization</subject><subject>Parathyroid Glands - enzymology</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>RNA - chemistry</subject><subject>RNA - genetics</subject><subject>Up-Regulation</subject><subject>Vertebrates: endocrinology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd1qFDEUxwdR7Fq981pyo1dOzdd8XZal3RaLLtqCdyGTnOlkzSbTZIZln8cn6Iv0mcywC70RDCSB8Du_c8g_y94TfEYowV826oxiXOSUFMWLbEEaXuQVaaqX2QJjSvKmor9OsjcxbjAmnBfsdXZCSoZZzZpF9uduyH_A_WTlaLxDvkNjD2gFDtCFU14bd4_WwY9gHPpqnIyAztHtfgB0_fSIjpU-7NHPqZ2cGVHivnmdXgO6SlgYrIxGzuK1DHLs98EbjVZWOh1neJ0agxsj2pmxR8s-eGdUEjtp0aU0dgrwNnvVSRvh3fE-ze4uL26XV_nN99X18vwmV7yqqrzVUtdQA-E1bhTDStKyqaWSrFWMUd0CVaqjbcHSR3S4pLoq67IBrlteQ9Gw0-zTwTsE_zBBHMXWRAU2zQp-iqKsyuRhxX9BimtOypIk8PMBVMHHGKATQzBbGfaCYDGnJzZKzOmJOb2Efzh6p3YL-hk-xpWAj0dARiVtF6RTJj5zFa-bpp5F_MDtvB0hxN922kEQPUg79gKnxcuqzlPnEqcD52mzKpWxQxk47VUwDoYAMYqNn0LKI_576r88wcVB</recordid><startdate>200602</startdate><enddate>200602</enddate><creator>Hibi, Yatsuka</creator><creator>Kambe, Fukushi</creator><creator>Tominaga, Yoshihiro</creator><creator>Mizuno, Yutaka</creator><creator>Kobayashi, Hironobu</creator><creator>Iwase, Katsumi</creator><creator>Imai, Tsuneo</creator><creator>Seo, Hisao</creator><general>Endocrine Society</general><general>Copyright by The Endocrine Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200602</creationdate><title>Up-Regulation of the Gene Encoding Protein Kinase A Type Iα Regulatory Subunit in Nodular Hyperplasia of Parathyroid Glands in Patients with Chronic Renal Failure</title><author>Hibi, Yatsuka ; Kambe, Fukushi ; Tominaga, Yoshihiro ; Mizuno, Yutaka ; Kobayashi, Hironobu ; Iwase, Katsumi ; Imai, Tsuneo ; Seo, Hisao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4777-bdad8e8e14809c30ca2698aca3bc332dbe2ccf2b53001f062d76869e4db48e593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Biological and medical sciences</topic><topic>Blotting, Northern</topic><topic>Blotting, Western</topic><topic>Cyclic AMP-Dependent Protein Kinase RIalpha Subunit</topic><topic>Cyclic AMP-Dependent Protein Kinases</topic><topic>Endocrinopathies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>Humans</topic><topic>Hyperparathyroidism, Secondary - complications</topic><topic>Hyperparathyroidism, Secondary - enzymology</topic><topic>Hyperparathyroidism, Secondary - genetics</topic><topic>Hyperparathyroidism, Secondary - pathology</topic><topic>Immunohistochemistry</topic><topic>Kidney Failure, Chronic - complications</topic><topic>Kidney Failure, Chronic - enzymology</topic><topic>Kidney Failure, Chronic - pathology</topic><topic>Medical sciences</topic><topic>Nucleic Acid Hybridization</topic><topic>Parathyroid Glands - enzymology</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>RNA - chemistry</topic><topic>RNA - genetics</topic><topic>Up-Regulation</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hibi, Yatsuka</creatorcontrib><creatorcontrib>Kambe, Fukushi</creatorcontrib><creatorcontrib>Tominaga, Yoshihiro</creatorcontrib><creatorcontrib>Mizuno, Yutaka</creatorcontrib><creatorcontrib>Kobayashi, Hironobu</creatorcontrib><creatorcontrib>Iwase, Katsumi</creatorcontrib><creatorcontrib>Imai, Tsuneo</creatorcontrib><creatorcontrib>Seo, Hisao</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hibi, Yatsuka</au><au>Kambe, Fukushi</au><au>Tominaga, Yoshihiro</au><au>Mizuno, Yutaka</au><au>Kobayashi, Hironobu</au><au>Iwase, Katsumi</au><au>Imai, Tsuneo</au><au>Seo, Hisao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Up-Regulation of the Gene Encoding Protein Kinase A Type Iα Regulatory Subunit in Nodular Hyperplasia of Parathyroid Glands in Patients with Chronic Renal Failure</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2006-02</date><risdate>2006</risdate><volume>91</volume><issue>2</issue><spage>563</spage><epage>568</epage><pages>563-568</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Context: Hyperplasia of parathyroid glands in patients with chronic renal failure is classified into diffuse (DH) and nodular (NH) types, and NH is often refractory to routine medical therapy.
Objective: Although it is considered that the parenchymal cells initially proliferate diffusely and then some of them are transformed to form nodules consisting of monoclonal cells, the underlying molecular mechanism for such a transformation is not fully understood. In this study we tried to identify the genes that are up-regulated in NH.
Design and Setting: The cDNA population prepared from DH was subtracted from that prepared from NH by a PCR-based cDNA subtraction method. The resultant cDNAs were cloned and sequenced. To confirm the up-regulation of the identified genes, a total of 35 parathyroid glands (18 DH, 16 NH, and one mixed) obtained from 21 patients were analyzed.
Results: One of the nuclear genes identified was the PRKAR1A gene, which encodes type Iα regulatory subunit (RIα) of cAMP-dependent protein kinase (PKA). Immunohistochemical analysis demonstrated that RIα was abundantly expressed in the nodular region, whereas the adjacent diffuse region displayed relatively low expression. Northern and Western blot analyses demonstrated up-regulation of RIα expression in most NH tested. Determination of PKA activities revealed that free PKA activities measured in the absence of cAMP in the assay were inversely correlated with RIα expression, indicating the functional significance of RIα up-regulation.
Conclusions: These results suggest that the aberrant expression of RIα is involved in the diffuse to nodular transformation of hyperplasia of parathyroid glands by impairing cAMP/PKA signal transduction.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>16303839</pmid><doi>10.1210/jc.2005-2155</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biological and medical sciences Blotting, Northern Blotting, Western Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Cyclic AMP-Dependent Protein Kinases Endocrinopathies Fundamental and applied biological sciences. Psychology Gene Expression Regulation, Enzymologic Humans Hyperparathyroidism, Secondary - complications Hyperparathyroidism, Secondary - enzymology Hyperparathyroidism, Secondary - genetics Hyperparathyroidism, Secondary - pathology Immunohistochemistry Kidney Failure, Chronic - complications Kidney Failure, Chronic - enzymology Kidney Failure, Chronic - pathology Medical sciences Nucleic Acid Hybridization Parathyroid Glands - enzymology Proteins - genetics Proteins - metabolism RNA - chemistry RNA - genetics Up-Regulation Vertebrates: endocrinology |
| title | Up-Regulation of the Gene Encoding Protein Kinase A Type Iα Regulatory Subunit in Nodular Hyperplasia of Parathyroid Glands in Patients with Chronic Renal Failure |
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