Ferritin Expression in Rat Hepatocytes and Kupffer Cells after Lead Nitrate Treatment
Lead nitrate induces hepatocyte proliferation and subsequent apoptosis in rat livers. Iron is a constituent of heme and is also required for cell proliferation. In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single...
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| Veröffentlicht in: | Toxicologic pathology 2009-02, Vol.37 (2), p.209-217 |
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| creator | Fan, Yang Yamada, Toshiyuki Shimizu, Takeshi Nanashima, Naoki Akita, Miki Suto, Kohji Tsuchida, Shigeki |
| description | Lead nitrate induces hepatocyte proliferation and subsequent apoptosis in rat livers. Iron is a constituent of heme and is also required for cell proliferation. In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single intravenous injection of lead nitrate. Western blotting and immunohistochemistry revealed that FTL was increased in hepatocytes around the central veins and strongly expressed in nonparenchymal cells. Some FTL-positive nonparenchymal cells were identified as Kupffer cells that were positive for CD68. FTL-positive Kupffer cells occupied about 60% of CD68-positive cells in the periportal and perivenous areas. The relationships between FTL expression and apoptosis induction or the engulfment of apoptotic cells were examined. TUNEL-positive cells were increased in the treatment group, and enhanced expression of milk fat globule EGF-like 8 was demonstrated in some Kupffer cells and hepatocytes, indicating enhanced apoptosis induction and phagocytosis of apoptotic cells. FTL-positive Kupffer cells were not detected without lead nitrate treatment or in rat livers treated with clofibrate, which induces hepatocyte proliferation but not apoptosis. These results suggest that FTL expression in Kupffer cells after lead treatment is dependent on phagocytosis of apoptotic cells. |
| doi_str_mv | 10.1177/0192623308328544 |
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Iron is a constituent of heme and is also required for cell proliferation. In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single intravenous injection of lead nitrate. Western blotting and immunohistochemistry revealed that FTL was increased in hepatocytes around the central veins and strongly expressed in nonparenchymal cells. Some FTL-positive nonparenchymal cells were identified as Kupffer cells that were positive for CD68. FTL-positive Kupffer cells occupied about 60% of CD68-positive cells in the periportal and perivenous areas. The relationships between FTL expression and apoptosis induction or the engulfment of apoptotic cells were examined. TUNEL-positive cells were increased in the treatment group, and enhanced expression of milk fat globule EGF-like 8 was demonstrated in some Kupffer cells and hepatocytes, indicating enhanced apoptosis induction and phagocytosis of apoptotic cells. FTL-positive Kupffer cells were not detected without lead nitrate treatment or in rat livers treated with clofibrate, which induces hepatocyte proliferation but not apoptosis. These results suggest that FTL expression in Kupffer cells after lead treatment is dependent on phagocytosis of apoptotic cells.</description><identifier>ISSN: 0192-6233</identifier><identifier>EISSN: 1533-1601</identifier><identifier>DOI: 10.1177/0192623308328544</identifier><identifier>PMID: 19332663</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Antigens, CD - metabolism ; Apoptosis - drug effects ; Biological and medical sciences ; Cell Proliferation - drug effects ; Chemical and industrial products toxicology. Toxic occupational diseases ; Ferritins - genetics ; Ferritins - metabolism ; Gene Expression - drug effects ; Hepatocytes - metabolism ; Immunohistochemistry ; In Situ Nick-End Labeling ; Kupffer Cells - metabolism ; Lead - pharmacology ; Lead - toxicity ; Male ; Medical sciences ; Metals and various inorganic compounds ; Nitrates - pharmacology ; Nitrates - toxicity ; Phagocytosis - drug effects ; Rats ; Rats, Sprague-Dawley ; Toxicology</subject><ispartof>Toxicologic pathology, 2009-02, Vol.37 (2), p.209-217</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-2a6a99e1d4103e727b104404fd207d84800a366d5cd7a878a8542d2b6a278aba3</citedby><cites>FETCH-LOGICAL-c439t-2a6a99e1d4103e727b104404fd207d84800a366d5cd7a878a8542d2b6a278aba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0192623308328544$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0192623308328544$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21274288$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19332663$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fan, Yang</creatorcontrib><creatorcontrib>Yamada, Toshiyuki</creatorcontrib><creatorcontrib>Shimizu, Takeshi</creatorcontrib><creatorcontrib>Nanashima, Naoki</creatorcontrib><creatorcontrib>Akita, Miki</creatorcontrib><creatorcontrib>Suto, Kohji</creatorcontrib><creatorcontrib>Tsuchida, Shigeki</creatorcontrib><title>Ferritin Expression in Rat Hepatocytes and Kupffer Cells after Lead Nitrate Treatment</title><title>Toxicologic pathology</title><addtitle>Toxicol Pathol</addtitle><description>Lead nitrate induces hepatocyte proliferation and subsequent apoptosis in rat livers. Iron is a constituent of heme and is also required for cell proliferation. In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single intravenous injection of lead nitrate. Western blotting and immunohistochemistry revealed that FTL was increased in hepatocytes around the central veins and strongly expressed in nonparenchymal cells. Some FTL-positive nonparenchymal cells were identified as Kupffer cells that were positive for CD68. FTL-positive Kupffer cells occupied about 60% of CD68-positive cells in the periportal and perivenous areas. The relationships between FTL expression and apoptosis induction or the engulfment of apoptotic cells were examined. TUNEL-positive cells were increased in the treatment group, and enhanced expression of milk fat globule EGF-like 8 was demonstrated in some Kupffer cells and hepatocytes, indicating enhanced apoptosis induction and phagocytosis of apoptotic cells. FTL-positive Kupffer cells were not detected without lead nitrate treatment or in rat livers treated with clofibrate, which induces hepatocyte proliferation but not apoptosis. These results suggest that FTL expression in Kupffer cells after lead treatment is dependent on phagocytosis of apoptotic cells.</description><subject>Animals</subject><subject>Antigens, CD - metabolism</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>Ferritins - genetics</subject><subject>Ferritins - metabolism</subject><subject>Gene Expression - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Kupffer Cells - metabolism</subject><subject>Lead - pharmacology</subject><subject>Lead - toxicity</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metals and various inorganic compounds</subject><subject>Nitrates - pharmacology</subject><subject>Nitrates - toxicity</subject><subject>Phagocytosis - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Toxicology</subject><issn>0192-6233</issn><issn>1533-1601</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtLw0AQxxdRbK3ePUku4im6r-xujlKqFYuC1HOYZCeS0iZxdwP227ulRUHwNK_fvP6EXDJ6y5jWd5TlXHEhqBHcZFIekTHLhEiZouyYjHfldFcfkTPvV5QywyQ9JSOWC8GVEmPy_oDONaFpk9lX79D7pmuTGL1BSObYQ-iqbUCfQGuT56Gva3TJFNfrmKlD9BcINnlpgoOAydIhhA224Zyc1LD2eHGwk7hntpzO08Xr49P0fpFWUuQh5aAgz5FZyahAzXXJqJRU1pZTbY00lIJQymaV1WC0gfgjt7xUwGNQgpiQm_3c3nWfA_pQbBpfxfOgxW7whZaK5Xlm8kjSPVm5znuHddG7ZgNuWzBa7LQs_moZW64Ow4dyg_a34SBeBK4PAPgK1rWDtmr8D8cZ15IbE7l0z3n4wGLVDa6Novy_-Bu-ZYdC</recordid><startdate>20090201</startdate><enddate>20090201</enddate><creator>Fan, Yang</creator><creator>Yamada, Toshiyuki</creator><creator>Shimizu, Takeshi</creator><creator>Nanashima, Naoki</creator><creator>Akita, Miki</creator><creator>Suto, Kohji</creator><creator>Tsuchida, Shigeki</creator><general>SAGE Publications</general><general>Sage Publications</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>7T5</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20090201</creationdate><title>Ferritin Expression in Rat Hepatocytes and Kupffer Cells after Lead Nitrate Treatment</title><author>Fan, Yang ; Yamada, Toshiyuki ; Shimizu, Takeshi ; Nanashima, Naoki ; Akita, Miki ; Suto, Kohji ; Tsuchida, Shigeki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-2a6a99e1d4103e727b104404fd207d84800a366d5cd7a878a8542d2b6a278aba3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antigens, CD - metabolism</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>Ferritins - genetics</topic><topic>Ferritins - metabolism</topic><topic>Gene Expression - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Kupffer Cells - metabolism</topic><topic>Lead - pharmacology</topic><topic>Lead - toxicity</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metals and various inorganic compounds</topic><topic>Nitrates - pharmacology</topic><topic>Nitrates - toxicity</topic><topic>Phagocytosis - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fan, Yang</creatorcontrib><creatorcontrib>Yamada, Toshiyuki</creatorcontrib><creatorcontrib>Shimizu, Takeshi</creatorcontrib><creatorcontrib>Nanashima, Naoki</creatorcontrib><creatorcontrib>Akita, Miki</creatorcontrib><creatorcontrib>Suto, Kohji</creatorcontrib><creatorcontrib>Tsuchida, Shigeki</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>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Toxicologic pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fan, Yang</au><au>Yamada, Toshiyuki</au><au>Shimizu, Takeshi</au><au>Nanashima, Naoki</au><au>Akita, Miki</au><au>Suto, Kohji</au><au>Tsuchida, Shigeki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ferritin Expression in Rat Hepatocytes and Kupffer Cells after Lead Nitrate Treatment</atitle><jtitle>Toxicologic pathology</jtitle><addtitle>Toxicol Pathol</addtitle><date>2009-02-01</date><risdate>2009</risdate><volume>37</volume><issue>2</issue><spage>209</spage><epage>217</epage><pages>209-217</pages><issn>0192-6233</issn><eissn>1533-1601</eissn><abstract>Lead nitrate induces hepatocyte proliferation and subsequent apoptosis in rat livers. Iron is a constituent of heme and is also required for cell proliferation. In this study, the expression of ferritin light-chain (FTL), the major iron storage protein, was investigated in rat livers after a single intravenous injection of lead nitrate. Western blotting and immunohistochemistry revealed that FTL was increased in hepatocytes around the central veins and strongly expressed in nonparenchymal cells. Some FTL-positive nonparenchymal cells were identified as Kupffer cells that were positive for CD68. FTL-positive Kupffer cells occupied about 60% of CD68-positive cells in the periportal and perivenous areas. The relationships between FTL expression and apoptosis induction or the engulfment of apoptotic cells were examined. TUNEL-positive cells were increased in the treatment group, and enhanced expression of milk fat globule EGF-like 8 was demonstrated in some Kupffer cells and hepatocytes, indicating enhanced apoptosis induction and phagocytosis of apoptotic cells. FTL-positive Kupffer cells were not detected without lead nitrate treatment or in rat livers treated with clofibrate, which induces hepatocyte proliferation but not apoptosis. These results suggest that FTL expression in Kupffer cells after lead treatment is dependent on phagocytosis of apoptotic cells.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>19332663</pmid><doi>10.1177/0192623308328544</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, CD - metabolism Apoptosis - drug effects Biological and medical sciences Cell Proliferation - drug effects Chemical and industrial products toxicology. Toxic occupational diseases Ferritins - genetics Ferritins - metabolism Gene Expression - drug effects Hepatocytes - metabolism Immunohistochemistry In Situ Nick-End Labeling Kupffer Cells - metabolism Lead - pharmacology Lead - toxicity Male Medical sciences Metals and various inorganic compounds Nitrates - pharmacology Nitrates - toxicity Phagocytosis - drug effects Rats Rats, Sprague-Dawley Toxicology |
| title | Ferritin Expression in Rat Hepatocytes and Kupffer Cells after Lead Nitrate Treatment |
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