Effects of lead and lead–melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats
Human lead (Pb) exposure induces many adverse health effects, including some related to lead accumulation in organs. Although lead bio-distribution in the body has been described, the molecular mechanism underlying distribution and excretion is not well understood. The transport of essential and tox...
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| Veröffentlicht in: | Biometals 2018-10, Vol.31 (5), p.859-871 |
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| creator | Soto-Arredondo, Karla J. Robles, Juvencio Díaz-Cervantes, Erik Ruiz-Ramírez, Carolina García-Revilla, Marco A. Wrobel, Katarzyna Wrobel, Kazimierz Díaz-Muñoz, Mauricio Méndez, Isabel Flores, Alberto Acevedo-Aguilar, Francisco Javier Martínez-Alfaro, Minerva |
| description | Human lead (Pb) exposure induces many adverse health effects, including some related to lead accumulation in organs. Although lead bio-distribution in the body has been described, the molecular mechanism underlying distribution and excretion is not well understood. The transport of essential and toxic metals is principally mediated by proteins. How lead affects the expression of metal transporter proteins in the principal metal excretory organs, i.e., the liver and kidney, is unknown. Considering that co-administration of melatonin and lead reduces the toxic effects of lead and lead levels in the blood in vivo, we examined how lead and co-administration of lead and melatonin affect the gene and protein expression of metal transporter proteins (ZIP8, ZIP14, CTR1 and DMT1) in these organs. Rats were exposed intraperitoneally to lead or lead-melatonin. Our results show that Pb exposure induces changes in the protein and gene expression of ZIP8, ZIP14 and CTR1. Alterations in the copper/zinc ratio found in the blood, liver and kidney were likely related to these changes. With DMT1 expression (gene and protein), a positive correlation was found with lead levels in the kidney. Co-administration of melatonin and lead reduced lead-induced DMT1 expression through an unknown mechanism. This effect of melatonin relates to reduced lead levels in the blood and kidney. The metal transport protein function and our results suggest that DMT1 likely contributes to lead accumulation in organs. These data further elucidate the effects of lead on Cu and Zn and the molecular mechanism underlying lead bio-distribution in animals. |
| doi_str_mv | 10.1007/s10534-018-0127-1 |
| format | Article |
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Although lead bio-distribution in the body has been described, the molecular mechanism underlying distribution and excretion is not well understood. The transport of essential and toxic metals is principally mediated by proteins. How lead affects the expression of metal transporter proteins in the principal metal excretory organs, i.e., the liver and kidney, is unknown. Considering that co-administration of melatonin and lead reduces the toxic effects of lead and lead levels in the blood in vivo, we examined how lead and co-administration of lead and melatonin affect the gene and protein expression of metal transporter proteins (ZIP8, ZIP14, CTR1 and DMT1) in these organs. Rats were exposed intraperitoneally to lead or lead-melatonin. Our results show that Pb exposure induces changes in the protein and gene expression of ZIP8, ZIP14 and CTR1. Alterations in the copper/zinc ratio found in the blood, liver and kidney were likely related to these changes. With DMT1 expression (gene and protein), a positive correlation was found with lead levels in the kidney. Co-administration of melatonin and lead reduced lead-induced DMT1 expression through an unknown mechanism. This effect of melatonin relates to reduced lead levels in the blood and kidney. The metal transport protein function and our results suggest that DMT1 likely contributes to lead accumulation in organs. These data further elucidate the effects of lead on Cu and Zn and the molecular mechanism underlying lead bio-distribution in animals.</description><identifier>ISSN: 0966-0844</identifier><identifier>EISSN: 1572-8773</identifier><identifier>DOI: 10.1007/s10534-018-0127-1</identifier><identifier>PMID: 30006888</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Accumulation ; Animals ; Biochemistry ; Biocompatibility ; Biomedical and Life Sciences ; Blood ; Carrier Proteins - biosynthesis ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell Biology ; Copper ; Copper - analysis ; Divalent metal transporter-1 ; Excretion ; Exposure ; Gene expression ; Gene Expression Regulation - drug effects ; Health risks ; Heavy metals ; Kidneys ; Lead ; Lead - analysis ; Lead - pharmacology ; Lead content ; Life Sciences ; Liver ; Male ; Mass Spectrometry ; Medicine/Public Health ; Melatonin ; Melatonin - analysis ; Melatonin - pharmacology ; Metals ; Microbiology ; Molecular chains ; Organs ; Pharmacology/Toxicology ; Plant Physiology ; Protein transport ; Proteins ; Rats ; Rats, Wistar ; Transport ; Zinc ; Zinc - analysis</subject><ispartof>Biometals, 2018-10, Vol.31 (5), p.859-871</ispartof><rights>Springer Nature B.V. 2018</rights><rights>BioMetals is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-98bac3a088ceb74156eaf67a47461f569e384da6489299e229d5910d919f86e3</citedby><cites>FETCH-LOGICAL-c372t-98bac3a088ceb74156eaf67a47461f569e384da6489299e229d5910d919f86e3</cites><orcidid>0000-0002-4874-3255</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10534-018-0127-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10534-018-0127-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30006888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Soto-Arredondo, Karla J.</creatorcontrib><creatorcontrib>Robles, Juvencio</creatorcontrib><creatorcontrib>Díaz-Cervantes, Erik</creatorcontrib><creatorcontrib>Ruiz-Ramírez, Carolina</creatorcontrib><creatorcontrib>García-Revilla, Marco A.</creatorcontrib><creatorcontrib>Wrobel, Katarzyna</creatorcontrib><creatorcontrib>Wrobel, Kazimierz</creatorcontrib><creatorcontrib>Díaz-Muñoz, Mauricio</creatorcontrib><creatorcontrib>Méndez, Isabel</creatorcontrib><creatorcontrib>Flores, Alberto</creatorcontrib><creatorcontrib>Acevedo-Aguilar, Francisco Javier</creatorcontrib><creatorcontrib>Martínez-Alfaro, Minerva</creatorcontrib><title>Effects of lead and lead–melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats</title><title>Biometals</title><addtitle>Biometals</addtitle><addtitle>Biometals</addtitle><description>Human lead (Pb) exposure induces many adverse health effects, including some related to lead accumulation in organs. Although lead bio-distribution in the body has been described, the molecular mechanism underlying distribution and excretion is not well understood. The transport of essential and toxic metals is principally mediated by proteins. How lead affects the expression of metal transporter proteins in the principal metal excretory organs, i.e., the liver and kidney, is unknown. Considering that co-administration of melatonin and lead reduces the toxic effects of lead and lead levels in the blood in vivo, we examined how lead and co-administration of lead and melatonin affect the gene and protein expression of metal transporter proteins (ZIP8, ZIP14, CTR1 and DMT1) in these organs. Rats were exposed intraperitoneally to lead or lead-melatonin. Our results show that Pb exposure induces changes in the protein and gene expression of ZIP8, ZIP14 and CTR1. Alterations in the copper/zinc ratio found in the blood, liver and kidney were likely related to these changes. With DMT1 expression (gene and protein), a positive correlation was found with lead levels in the kidney. Co-administration of melatonin and lead reduced lead-induced DMT1 expression through an unknown mechanism. This effect of melatonin relates to reduced lead levels in the blood and kidney. The metal transport protein function and our results suggest that DMT1 likely contributes to lead accumulation in organs. These data further elucidate the effects of lead on Cu and Zn and the molecular mechanism underlying lead bio-distribution in animals.</description><subject>Accumulation</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biocompatibility</subject><subject>Biomedical and Life Sciences</subject><subject>Blood</subject><subject>Carrier Proteins - biosynthesis</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell Biology</subject><subject>Copper</subject><subject>Copper - analysis</subject><subject>Divalent metal transporter-1</subject><subject>Excretion</subject><subject>Exposure</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Health risks</subject><subject>Heavy metals</subject><subject>Kidneys</subject><subject>Lead</subject><subject>Lead - analysis</subject><subject>Lead - pharmacology</subject><subject>Lead content</subject><subject>Life Sciences</subject><subject>Liver</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Medicine/Public Health</subject><subject>Melatonin</subject><subject>Melatonin - analysis</subject><subject>Melatonin - pharmacology</subject><subject>Metals</subject><subject>Microbiology</subject><subject>Molecular chains</subject><subject>Organs</subject><subject>Pharmacology/Toxicology</subject><subject>Plant Physiology</subject><subject>Protein transport</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Transport</subject><subject>Zinc</subject><subject>Zinc - 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of lead and lead–melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats</title><author>Soto-Arredondo, Karla J. ; Robles, Juvencio ; Díaz-Cervantes, Erik ; Ruiz-Ramírez, Carolina ; García-Revilla, Marco A. ; Wrobel, Katarzyna ; Wrobel, Kazimierz ; Díaz-Muñoz, Mauricio ; Méndez, Isabel ; Flores, Alberto ; Acevedo-Aguilar, Francisco Javier ; Martínez-Alfaro, Minerva</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-98bac3a088ceb74156eaf67a47461f569e384da6489299e229d5910d919f86e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Accumulation</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biocompatibility</topic><topic>Biomedical and Life Sciences</topic><topic>Blood</topic><topic>Carrier Proteins - biosynthesis</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - 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Alberto</au><au>Acevedo-Aguilar, Francisco Javier</au><au>Martínez-Alfaro, Minerva</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of lead and lead–melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats</atitle><jtitle>Biometals</jtitle><stitle>Biometals</stitle><addtitle>Biometals</addtitle><date>2018-10-01</date><risdate>2018</risdate><volume>31</volume><issue>5</issue><spage>859</spage><epage>871</epage><pages>859-871</pages><issn>0966-0844</issn><eissn>1572-8773</eissn><abstract>Human lead (Pb) exposure induces many adverse health effects, including some related to lead accumulation in organs. Although lead bio-distribution in the body has been described, the molecular mechanism underlying distribution and excretion is not well understood. The transport of essential and toxic metals is principally mediated by proteins. How lead affects the expression of metal transporter proteins in the principal metal excretory organs, i.e., the liver and kidney, is unknown. Considering that co-administration of melatonin and lead reduces the toxic effects of lead and lead levels in the blood in vivo, we examined how lead and co-administration of lead and melatonin affect the gene and protein expression of metal transporter proteins (ZIP8, ZIP14, CTR1 and DMT1) in these organs. Rats were exposed intraperitoneally to lead or lead-melatonin. Our results show that Pb exposure induces changes in the protein and gene expression of ZIP8, ZIP14 and CTR1. Alterations in the copper/zinc ratio found in the blood, liver and kidney were likely related to these changes. With DMT1 expression (gene and protein), a positive correlation was found with lead levels in the kidney. Co-administration of melatonin and lead reduced lead-induced DMT1 expression through an unknown mechanism. This effect of melatonin relates to reduced lead levels in the blood and kidney. The metal transport protein function and our results suggest that DMT1 likely contributes to lead accumulation in organs. These data further elucidate the effects of lead on Cu and Zn and the molecular mechanism underlying lead bio-distribution in animals.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>30006888</pmid><doi>10.1007/s10534-018-0127-1</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-4874-3255</orcidid></addata></record> |
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| subjects | Accumulation Animals Biochemistry Biocompatibility Biomedical and Life Sciences Blood Carrier Proteins - biosynthesis Carrier Proteins - genetics Carrier Proteins - metabolism Cell Biology Copper Copper - analysis Divalent metal transporter-1 Excretion Exposure Gene expression Gene Expression Regulation - drug effects Health risks Heavy metals Kidneys Lead Lead - analysis Lead - pharmacology Lead content Life Sciences Liver Male Mass Spectrometry Medicine/Public Health Melatonin Melatonin - analysis Melatonin - pharmacology Metals Microbiology Molecular chains Organs Pharmacology/Toxicology Plant Physiology Protein transport Proteins Rats Rats, Wistar Transport Zinc Zinc - analysis |
| title | Effects of lead and lead–melatonin exposure on protein and gene expression of metal transporters, proteins and the copper/zinc ratio in rats |
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