COMP-Ang1, Angiopoietin-1 Variant Protects Radiation-Induced Bone Marrow Damage in C57BL/6 Mice
Angiopoietin-1 (Ang1) is a vasculogenic factor which is signaled through the endothelial and bone marrow cell-specific, Tie2 receptor tyrosine kinase and has potential therapeutic applications for the induction of angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. In...
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| Veröffentlicht in: | JOURNAL OF RADIATION RESEARCH 2008-05, Vol.49 (3), p.313-320 |
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| creator | Lee, Hae June Bae, Sang Woo Koh, Gou Young Lee, Yun Sil |
| description | Angiopoietin-1 (Ang1) is a vasculogenic factor which is signaled through the endothelial and bone marrow cell-specific, Tie2 receptor tyrosine kinase and has potential therapeutic applications for the induction of angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. In this study, we examined whether Ang1 directly exhibits bone marrow protection after ionizing radiation (IR) using an adenoviral vector of COMP-Ang1 (Ad-COMP-Ang1). This is a variant of Ang1 by replacement of the Nterminal portion of Ang1 with short coiled-coil domains of cartilage oligomeric matrix protein-Angiopoietin 1 (COMP-Ang1) which are, long enough for oligomerization but short enough to avoid problems of aggregation and insolubility. A spleen colony assay after 4.5 Gy whole body radiation, indicated that COMP-Ang1 significantly increased the mean colony numbers. Both the decrease in bone marrow cellularity and increased TUNEL (Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling) positive cells produced by radiation in bone marrow were significantly inhibited by COMP-Ang1 transfer. The expression of the ligands of Ang1 and Tie2 receptors were increased by radiation and, the COMPAng1 transfer potentiated this protein expression. Pre-treatment of Ang1 could be beneficial in protecting bone marrow from damage by radiation and COMP-Ang1 may be an effective alternative to native Ang1 for therapeutic purposes. |
| doi_str_mv | 10.1269/jrr.07064 |
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In this study, we examined whether Ang1 directly exhibits bone marrow protection after ionizing radiation (IR) using an adenoviral vector of COMP-Ang1 (Ad-COMP-Ang1). This is a variant of Ang1 by replacement of the Nterminal portion of Ang1 with short coiled-coil domains of cartilage oligomeric matrix protein-Angiopoietin 1 (COMP-Ang1) which are, long enough for oligomerization but short enough to avoid problems of aggregation and insolubility. A spleen colony assay after 4.5 Gy whole body radiation, indicated that COMP-Ang1 significantly increased the mean colony numbers. Both the decrease in bone marrow cellularity and increased TUNEL (Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling) positive cells produced by radiation in bone marrow were significantly inhibited by COMP-Ang1 transfer. The expression of the ligands of Ang1 and Tie2 receptors were increased by radiation and, the COMPAng1 transfer potentiated this protein expression. Pre-treatment of Ang1 could be beneficial in protecting bone marrow from damage by radiation and COMP-Ang1 may be an effective alternative to native Ang1 for therapeutic purposes.</description><identifier>ISSN: 0449-3060</identifier><identifier>ISSN: 1349-9157</identifier><identifier>EISSN: 1349-9157</identifier><identifier>DOI: 10.1269/jrr.07064</identifier><identifier>PMID: 18413981</identifier><language>eng</language><publisher>England: THE JAPAN RADIATION RESEARCH SOCIETY</publisher><subject>Adenoviridae - genetics ; Angiogenesis ; Angiopoietin-1 - chemistry ; Angiopoietin-1 - pharmacology ; Animals ; Bone marrow ; Bone Marrow - radiation effects ; Cartilage ; Cell survival ; Colonies ; Colony-Forming Units Assay ; DNA nucleotidylexotransferase ; Endothelial cells ; Expression vectors ; Female ; Genetic Vectors ; Health aspects ; House mouse ; In Situ Nick-End Labeling ; Ionizing radiation ; Leakage ; Male ; Mice ; Mice, Inbred C57BL ; Oligomerization ; Protein-tyrosine kinase receptors ; Radiation Protection - methods ; Spleen ; Therapeutic applications ; Transfection</subject><ispartof>JOURNAL OF RADIATION RESEARCH, 2008-05, Vol.49 (3), p.313-320</ispartof><rights>COPYRIGHT 2008 Oxford University Press</rights><rights>Copyright Japan Science and Technology Agency 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c727t-993fc6b970b324b196635c513e8ea2483ecda53a449b42c9cc17efacadd80d403</citedby><cites>FETCH-LOGICAL-c727t-993fc6b970b324b196635c513e8ea2483ecda53a449b42c9cc17efacadd80d403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18413981$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hae June</creatorcontrib><creatorcontrib>Bae, Sang Woo</creatorcontrib><creatorcontrib>Koh, Gou Young</creatorcontrib><creatorcontrib>Lee, Yun Sil</creatorcontrib><creatorcontrib>Korea Institute of Radiological and Medical Sciences</creatorcontrib><creatorcontrib>Biomedical Research Center and Department of Biological Sciences</creatorcontrib><creatorcontrib>Korea Advanced Institute of Science and Technology</creatorcontrib><creatorcontrib>Korea</creatorcontrib><creatorcontrib>Division of Radiation Effect</creatorcontrib><title>COMP-Ang1, Angiopoietin-1 Variant Protects Radiation-Induced Bone Marrow Damage in C57BL/6 Mice</title><title>JOURNAL OF RADIATION RESEARCH</title><addtitle>J Radiat Res</addtitle><description>Angiopoietin-1 (Ang1) is a vasculogenic factor which is signaled through the endothelial and bone marrow cell-specific, Tie2 receptor tyrosine kinase and has potential therapeutic applications for the induction of angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. 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Pre-treatment of Ang1 could be beneficial in protecting bone marrow from damage by radiation and COMP-Ang1 may be an effective alternative to native Ang1 for therapeutic purposes.</description><subject>Adenoviridae - genetics</subject><subject>Angiogenesis</subject><subject>Angiopoietin-1 - chemistry</subject><subject>Angiopoietin-1 - pharmacology</subject><subject>Animals</subject><subject>Bone marrow</subject><subject>Bone Marrow - radiation effects</subject><subject>Cartilage</subject><subject>Cell survival</subject><subject>Colonies</subject><subject>Colony-Forming Units Assay</subject><subject>DNA nucleotidylexotransferase</subject><subject>Endothelial cells</subject><subject>Expression vectors</subject><subject>Female</subject><subject>Genetic Vectors</subject><subject>Health aspects</subject><subject>House mouse</subject><subject>In Situ Nick-End Labeling</subject><subject>Ionizing radiation</subject><subject>Leakage</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Oligomerization</subject><subject>Protein-tyrosine kinase receptors</subject><subject>Radiation Protection - methods</subject><subject>Spleen</subject><subject>Therapeutic applications</subject><subject>Transfection</subject><issn>0449-3060</issn><issn>1349-9157</issn><issn>1349-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVFr2zAUhcXYWEPXh_2BIRiMFeb0XkmWrcc067ZCQsvY9ipkWQ7KHCmVbcb-fZUmUNjDHnQlpE-Xc-4h5C3CHJlUV9uU5lCBFC_IDLlQhcKyeklmIPKZg4QzcjEMvgEsJUCN-JqcYS2QqxpnRC_v1vfFImzwE83Vx330bvShQPrLJG_CSO9THJ0dB_rdtN6MPobiNrSTdS29jsHRtUkp_qGfzc5sHPWBLsvqenUl6dpb94a86kw_uIvTfk5-frn5sfxWrO6-3i4Xq8JWrBoLpXhnZaMqaDgTDSopeWlL5K52homaO9uakpvsqRHMKmuxcp2xpm1raAXwc_Lh2Hef4sPkhlHv_GBd35vg4jRoBoqhhDqDH_8LIme8hrJih57v_0G3cUoh29AoshIhWcUyNT9SG9M77UMXx5SFZWlu520eUOfz_aLkEksh-EHB5fGDTXEYkuv0PvmdSX81gj5EqnOk-inSzL47SZianWufyVOAGbg5AvnVW9PH0PvgnoXa33IbU3J5AFBrAKGAa8C8-FNhkD3kYT8CGoqtkg</recordid><startdate>20080501</startdate><enddate>20080501</enddate><creator>Lee, Hae June</creator><creator>Bae, Sang Woo</creator><creator>Koh, Gou Young</creator><creator>Lee, Yun Sil</creator><general>THE JAPAN RADIATION RESEARCH SOCIETY</general><general>Oxford University Press</general><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>K9.</scope><scope>7U7</scope><scope>C1K</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20080501</creationdate><title>COMP-Ang1, Angiopoietin-1 Variant Protects Radiation-Induced Bone Marrow Damage in C57BL/6 Mice</title><author>Lee, Hae June ; Bae, Sang Woo ; Koh, Gou Young ; Lee, Yun Sil</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c727t-993fc6b970b324b196635c513e8ea2483ecda53a449b42c9cc17efacadd80d403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenoviridae - genetics</topic><topic>Angiogenesis</topic><topic>Angiopoietin-1 - chemistry</topic><topic>Angiopoietin-1 - pharmacology</topic><topic>Animals</topic><topic>Bone marrow</topic><topic>Bone Marrow - radiation effects</topic><topic>Cartilage</topic><topic>Cell survival</topic><topic>Colonies</topic><topic>Colony-Forming Units Assay</topic><topic>DNA nucleotidylexotransferase</topic><topic>Endothelial cells</topic><topic>Expression vectors</topic><topic>Female</topic><topic>Genetic Vectors</topic><topic>Health aspects</topic><topic>House mouse</topic><topic>In Situ Nick-End Labeling</topic><topic>Ionizing radiation</topic><topic>Leakage</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Oligomerization</topic><topic>Protein-tyrosine kinase receptors</topic><topic>Radiation Protection - methods</topic><topic>Spleen</topic><topic>Therapeutic applications</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Hae June</creatorcontrib><creatorcontrib>Bae, Sang Woo</creatorcontrib><creatorcontrib>Koh, Gou Young</creatorcontrib><creatorcontrib>Lee, Yun Sil</creatorcontrib><creatorcontrib>Korea Institute of Radiological and Medical Sciences</creatorcontrib><creatorcontrib>Biomedical Research Center and Department of Biological Sciences</creatorcontrib><creatorcontrib>Korea Advanced Institute of Science and Technology</creatorcontrib><creatorcontrib>Korea</creatorcontrib><creatorcontrib>Division of Radiation Effect</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>JOURNAL OF RADIATION RESEARCH</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Hae June</au><au>Bae, Sang Woo</au><au>Koh, Gou Young</au><au>Lee, Yun Sil</au><aucorp>Korea Institute of Radiological and Medical Sciences</aucorp><aucorp>Biomedical Research Center and Department of Biological Sciences</aucorp><aucorp>Korea Advanced Institute of Science and Technology</aucorp><aucorp>Korea</aucorp><aucorp>Division of Radiation Effect</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>COMP-Ang1, Angiopoietin-1 Variant Protects Radiation-Induced Bone Marrow Damage in C57BL/6 Mice</atitle><jtitle>JOURNAL OF RADIATION RESEARCH</jtitle><addtitle>J Radiat Res</addtitle><date>2008-05-01</date><risdate>2008</risdate><volume>49</volume><issue>3</issue><spage>313</spage><epage>320</epage><pages>313-320</pages><issn>0449-3060</issn><issn>1349-9157</issn><eissn>1349-9157</eissn><abstract>Angiopoietin-1 (Ang1) is a vasculogenic factor which is signaled through the endothelial and bone marrow cell-specific, Tie2 receptor tyrosine kinase and has potential therapeutic applications for the induction of angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. In this study, we examined whether Ang1 directly exhibits bone marrow protection after ionizing radiation (IR) using an adenoviral vector of COMP-Ang1 (Ad-COMP-Ang1). This is a variant of Ang1 by replacement of the Nterminal portion of Ang1 with short coiled-coil domains of cartilage oligomeric matrix protein-Angiopoietin 1 (COMP-Ang1) which are, long enough for oligomerization but short enough to avoid problems of aggregation and insolubility. A spleen colony assay after 4.5 Gy whole body radiation, indicated that COMP-Ang1 significantly increased the mean colony numbers. Both the decrease in bone marrow cellularity and increased TUNEL (Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling) positive cells produced by radiation in bone marrow were significantly inhibited by COMP-Ang1 transfer. The expression of the ligands of Ang1 and Tie2 receptors were increased by radiation and, the COMPAng1 transfer potentiated this protein expression. Pre-treatment of Ang1 could be beneficial in protecting bone marrow from damage by radiation and COMP-Ang1 may be an effective alternative to native Ang1 for therapeutic purposes.</abstract><cop>England</cop><pub>THE JAPAN RADIATION RESEARCH SOCIETY</pub><pmid>18413981</pmid><doi>10.1269/jrr.07064</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoviridae - genetics Angiogenesis Angiopoietin-1 - chemistry Angiopoietin-1 - pharmacology Animals Bone marrow Bone Marrow - radiation effects Cartilage Cell survival Colonies Colony-Forming Units Assay DNA nucleotidylexotransferase Endothelial cells Expression vectors Female Genetic Vectors Health aspects House mouse In Situ Nick-End Labeling Ionizing radiation Leakage Male Mice Mice, Inbred C57BL Oligomerization Protein-tyrosine kinase receptors Radiation Protection - methods Spleen Therapeutic applications Transfection |
| title | COMP-Ang1, Angiopoietin-1 Variant Protects Radiation-Induced Bone Marrow Damage in C57BL/6 Mice |
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