The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells
Swainsonine (SW) is the principal toxic ingredient of locoweeds, which can cause intensive vacuolar degeneration because of α-mannosidase inhibition after animal ingestion. While SW can lead to obvious liver damage in vivo, the mechanism of hepatotoxic damage caused by SW is not clear. Therefore, BR...
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| Veröffentlicht in: | Toxicon (Oxford) 2015-06, Vol.99, p.44-50 |
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| creator | Lu, Hao Ma, Feng Wang, Huan Geng, Peng-shuai Wang, Shan-shan Wang, Jian-guo Wu, Chen-chen Zhao, Bao-yu |
| description | Swainsonine (SW) is the principal toxic ingredient of locoweeds, which can cause intensive vacuolar degeneration because of α-mannosidase inhibition after animal ingestion. While SW can lead to obvious liver damage in vivo, the mechanism of hepatotoxic damage caused by SW is not clear. Therefore, BRL-3A cells were treated for 24, 48, and 72 h with SW at various concentrations (0, 700, 900, 1100 μg/mL). The α-mannosidase (AMAN) activity was determined in BRL-3A cells using an enzyme substrate technique. The expression of mRNA and proteins of GM II (MAN2A1) and LAM (MAN2B1) in BRL-3A cells was detected by qPCR and Western-blot. The results showed that SW could significantly reduce the activity of AMAN in a time-dose effect relationship. Compared with the control group, the activity of AMAN significantly decreased only in the group treated with 1100 μg/mL SW for 24 h (P |
| doi_str_mv | 10.1016/j.toxicon.2015.03.008 |
| format | Article |
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•The effect of swainsonine on the activity and expression of α-mannosidase in hepatic cells was observed for the first time.•Swainsonine caused the damage of liver tissues through inhibiting the activity and expression of α-mannosidase in hepatic cells.</description><identifier>ISSN: 0041-0101</identifier><identifier>EISSN: 1879-3150</identifier><identifier>DOI: 10.1016/j.toxicon.2015.03.008</identifier><identifier>PMID: 25797317</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>alpha-Mannosidase - antagonists & inhibitors ; alpha-Mannosidase - genetics ; alpha-Mannosidase - metabolism ; Animals ; Biocompatibility ; Biomedical materials ; BRL-3A cells ; Cell Line ; Cell Survival - drug effects ; China ; Damage ; Enzyme Repression - drug effects ; Gene expression ; Golgi Apparatus - drug effects ; Golgi Apparatus - enzymology ; Hepatocytes - drug effects ; Hepatocytes - enzymology ; Hepatocytes - metabolism ; In vivo testing ; In vivo tests ; Inhibition ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - genetics ; Isoenzymes - metabolism ; Kinetics ; Locoweed ; Lysosomes - drug effects ; Lysosomes - enzymology ; MAN2A1 ; MAN2B1 ; Oxytropis - chemistry ; Proteins ; Rats ; RNA, Messenger - metabolism ; Swainsonine ; Swainsonine - toxicity ; Toxins, Biological - toxicity</subject><ispartof>Toxicon (Oxford), 2015-06, Vol.99, p.44-50</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-83791d708d1490f8b00835f7a45c05cb83cf009facabcde26643077623a4bb5c3</citedby><cites>FETCH-LOGICAL-c431t-83791d708d1490f8b00835f7a45c05cb83cf009facabcde26643077623a4bb5c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0041010115000707$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25797317$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Hao</creatorcontrib><creatorcontrib>Ma, Feng</creatorcontrib><creatorcontrib>Wang, Huan</creatorcontrib><creatorcontrib>Geng, Peng-shuai</creatorcontrib><creatorcontrib>Wang, Shan-shan</creatorcontrib><creatorcontrib>Wang, Jian-guo</creatorcontrib><creatorcontrib>Wu, Chen-chen</creatorcontrib><creatorcontrib>Zhao, Bao-yu</creatorcontrib><title>The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells</title><title>Toxicon (Oxford)</title><addtitle>Toxicon</addtitle><description>Swainsonine (SW) is the principal toxic ingredient of locoweeds, which can cause intensive vacuolar degeneration because of α-mannosidase inhibition after animal ingestion. While SW can lead to obvious liver damage in vivo, the mechanism of hepatotoxic damage caused by SW is not clear. Therefore, BRL-3A cells were treated for 24, 48, and 72 h with SW at various concentrations (0, 700, 900, 1100 μg/mL). The α-mannosidase (AMAN) activity was determined in BRL-3A cells using an enzyme substrate technique. The expression of mRNA and proteins of GM II (MAN2A1) and LAM (MAN2B1) in BRL-3A cells was detected by qPCR and Western-blot. The results showed that SW could significantly reduce the activity of AMAN in a time-dose effect relationship. Compared with the control group, the activity of AMAN significantly decreased only in the group treated with 1100 μg/mL SW for 24 h (P < 0.01), but the activity decreased significantly (P < 0.05 or P < 0.01) in all experimental groups treated for 48 or 72 h. SW also significantly reduced the expression of MAN2A1 and MAN2B1 mRNA and proteins in a time-dose effect relationship (P < 0.05 or P < 0.01), while the inhibition of SW was stronger for MAN2B1 than for MAN2A1. These results suggest that SW can significantly reduce the activity and expression of α-mannosidase thus causing SW-induced hepatotoxic damage.
•The effect of swainsonine on the activity and expression of α-mannosidase in hepatic cells was observed for the first time.•Swainsonine caused the damage of liver tissues through inhibiting the activity and expression of α-mannosidase in hepatic cells.</description><subject>alpha-Mannosidase - antagonists & inhibitors</subject><subject>alpha-Mannosidase - genetics</subject><subject>alpha-Mannosidase - metabolism</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>BRL-3A cells</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>China</subject><subject>Damage</subject><subject>Enzyme Repression - drug effects</subject><subject>Gene expression</subject><subject>Golgi Apparatus - drug effects</subject><subject>Golgi Apparatus - enzymology</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - enzymology</subject><subject>Hepatocytes - metabolism</subject><subject>In vivo testing</subject><subject>In vivo tests</subject><subject>Inhibition</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - genetics</subject><subject>Isoenzymes - metabolism</subject><subject>Kinetics</subject><subject>Locoweed</subject><subject>Lysosomes - drug effects</subject><subject>Lysosomes - enzymology</subject><subject>MAN2A1</subject><subject>MAN2B1</subject><subject>Oxytropis - chemistry</subject><subject>Proteins</subject><subject>Rats</subject><subject>RNA, Messenger - metabolism</subject><subject>Swainsonine</subject><subject>Swainsonine - toxicity</subject><subject>Toxins, Biological - toxicity</subject><issn>0041-0101</issn><issn>1879-3150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkcFOGzEQhq2qqITAI7TysZddxuv12j5VFLWAFKkSghMHy-sdq44SO11vKDwWL9JnqqOkvcJpDvPN_P_MT8hHBjUD1p0v6yk9BZdi3QATNfAaQL0jM6akrjgT8J7MAFpWQcGPyUnOSwDgSncfyHEjpJacyRl5uPuJFL1HN2WaPM2_bYg5xRCRpkin0rVuCo9heqY2DhSfNiPmHEqv0H9eqrWNMeUw2Iw0RPr1dlHxC-pwtcqn5MjbVcazQ52T--_f7i6vq8WPq5vLi0XlWs6mSnGp2SBBDazV4FVfDuHCS9sKB8L1ijsPoL11tncDNl3XcpCya7ht-144Pief93s3Y_q1xTyZdcg7BzZi2mbDpATeKi3aN6C8UUxrBQUVe9SNKecRvdmMYW3HZ8PA7CIwS3OIwOwiMMDNzvmcfDpIbPs1Dv-n_v28AF_2AJafPAYcTXYBo8MhjCUGM6TwisRfVZ2aDA</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Lu, Hao</creator><creator>Ma, Feng</creator><creator>Wang, Huan</creator><creator>Geng, Peng-shuai</creator><creator>Wang, Shan-shan</creator><creator>Wang, Jian-guo</creator><creator>Wu, Chen-chen</creator><creator>Zhao, Bao-yu</creator><general>Elsevier Ltd</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>7U7</scope><scope>C1K</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope></search><sort><creationdate>20150601</creationdate><title>The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells</title><author>Lu, Hao ; Ma, Feng ; Wang, Huan ; Geng, Peng-shuai ; Wang, Shan-shan ; Wang, Jian-guo ; Wu, Chen-chen ; Zhao, Bao-yu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-83791d708d1490f8b00835f7a45c05cb83cf009facabcde26643077623a4bb5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>alpha-Mannosidase - antagonists & inhibitors</topic><topic>alpha-Mannosidase - genetics</topic><topic>alpha-Mannosidase - metabolism</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>BRL-3A cells</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>China</topic><topic>Damage</topic><topic>Enzyme Repression - drug effects</topic><topic>Gene expression</topic><topic>Golgi Apparatus - drug effects</topic><topic>Golgi Apparatus - enzymology</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - enzymology</topic><topic>Hepatocytes - metabolism</topic><topic>In vivo testing</topic><topic>In vivo tests</topic><topic>Inhibition</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Isoenzymes - genetics</topic><topic>Isoenzymes - metabolism</topic><topic>Kinetics</topic><topic>Locoweed</topic><topic>Lysosomes - drug effects</topic><topic>Lysosomes - enzymology</topic><topic>MAN2A1</topic><topic>MAN2B1</topic><topic>Oxytropis - chemistry</topic><topic>Proteins</topic><topic>Rats</topic><topic>RNA, Messenger - metabolism</topic><topic>Swainsonine</topic><topic>Swainsonine - toxicity</topic><topic>Toxins, Biological - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Hao</creatorcontrib><creatorcontrib>Ma, Feng</creatorcontrib><creatorcontrib>Wang, Huan</creatorcontrib><creatorcontrib>Geng, Peng-shuai</creatorcontrib><creatorcontrib>Wang, Shan-shan</creatorcontrib><creatorcontrib>Wang, Jian-guo</creatorcontrib><creatorcontrib>Wu, Chen-chen</creatorcontrib><creatorcontrib>Zhao, Bao-yu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Toxicon (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Hao</au><au>Ma, Feng</au><au>Wang, Huan</au><au>Geng, Peng-shuai</au><au>Wang, Shan-shan</au><au>Wang, Jian-guo</au><au>Wu, Chen-chen</au><au>Zhao, Bao-yu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells</atitle><jtitle>Toxicon (Oxford)</jtitle><addtitle>Toxicon</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>99</volume><spage>44</spage><epage>50</epage><pages>44-50</pages><issn>0041-0101</issn><eissn>1879-3150</eissn><abstract>Swainsonine (SW) is the principal toxic ingredient of locoweeds, which can cause intensive vacuolar degeneration because of α-mannosidase inhibition after animal ingestion. While SW can lead to obvious liver damage in vivo, the mechanism of hepatotoxic damage caused by SW is not clear. Therefore, BRL-3A cells were treated for 24, 48, and 72 h with SW at various concentrations (0, 700, 900, 1100 μg/mL). The α-mannosidase (AMAN) activity was determined in BRL-3A cells using an enzyme substrate technique. The expression of mRNA and proteins of GM II (MAN2A1) and LAM (MAN2B1) in BRL-3A cells was detected by qPCR and Western-blot. The results showed that SW could significantly reduce the activity of AMAN in a time-dose effect relationship. Compared with the control group, the activity of AMAN significantly decreased only in the group treated with 1100 μg/mL SW for 24 h (P < 0.01), but the activity decreased significantly (P < 0.05 or P < 0.01) in all experimental groups treated for 48 or 72 h. SW also significantly reduced the expression of MAN2A1 and MAN2B1 mRNA and proteins in a time-dose effect relationship (P < 0.05 or P < 0.01), while the inhibition of SW was stronger for MAN2B1 than for MAN2A1. These results suggest that SW can significantly reduce the activity and expression of α-mannosidase thus causing SW-induced hepatotoxic damage.
•The effect of swainsonine on the activity and expression of α-mannosidase in hepatic cells was observed for the first time.•Swainsonine caused the damage of liver tissues through inhibiting the activity and expression of α-mannosidase in hepatic cells.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>25797317</pmid><doi>10.1016/j.toxicon.2015.03.008</doi><tpages>7</tpages></addata></record> |
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| subjects | alpha-Mannosidase - antagonists & inhibitors alpha-Mannosidase - genetics alpha-Mannosidase - metabolism Animals Biocompatibility Biomedical materials BRL-3A cells Cell Line Cell Survival - drug effects China Damage Enzyme Repression - drug effects Gene expression Golgi Apparatus - drug effects Golgi Apparatus - enzymology Hepatocytes - drug effects Hepatocytes - enzymology Hepatocytes - metabolism In vivo testing In vivo tests Inhibition Isoenzymes - antagonists & inhibitors Isoenzymes - genetics Isoenzymes - metabolism Kinetics Locoweed Lysosomes - drug effects Lysosomes - enzymology MAN2A1 MAN2B1 Oxytropis - chemistry Proteins Rats RNA, Messenger - metabolism Swainsonine Swainsonine - toxicity Toxins, Biological - toxicity |
| title | The effects of swainsonine on the activity and expression of α-mannosidase in BRL-3A cells |
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