Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts
Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a prote...
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| creator | Rodrigues, Gabriela Gomes Cardoso Dellê, Humberto Brito, Rodrigo Barbosa Oliveira Cardoso, Vinícius Oliveira Fernandes, Kristianne Porta Santos Mesquita-Ferrari, Raquel Agnelli Cunha, Regiane Stafim Stinghen, Andréa Emilia Marques Dalboni, Maria Aparecida Barreto, Fellype Carvalho |
| description | Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia.
Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry.
Myoblast viability was reduced by IS236 in a time-dependent pattern (p |
| doi_str_mv | 10.1016/j.arcmed.2019.12.020 |
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Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry.
Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment.
These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.
Myoblast viability was significantly reduced by IS236 in a time-dependent pattern (p <0.05; 84.4%, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48 h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72 h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation, at any IS concentration tested or time-point experiment. These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia. [Display omitted]]]></description><identifier>ISSN: 0188-4409</identifier><identifier>EISSN: 1873-5487</identifier><identifier>DOI: 10.1016/j.arcmed.2019.12.020</identifier><identifier>PMID: 32086105</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Chronic kidney disease ; Indoxyl sulfate ; Sarcopenia</subject><ispartof>Archives of medical research, 2020-01, Vol.51 (1), p.21-29</ispartof><rights>2020 IMSS</rights><rights>Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c428t-354f9fa02099c372f8518af7a9b133ab0a57fa36eab040f3446744dd4a5949743</citedby><cites>FETCH-LOGICAL-c428t-354f9fa02099c372f8518af7a9b133ab0a57fa36eab040f3446744dd4a5949743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.arcmed.2019.12.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32086105$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodrigues, Gabriela Gomes Cardoso</creatorcontrib><creatorcontrib>Dellê, Humberto</creatorcontrib><creatorcontrib>Brito, Rodrigo Barbosa Oliveira</creatorcontrib><creatorcontrib>Cardoso, Vinícius Oliveira</creatorcontrib><creatorcontrib>Fernandes, Kristianne Porta Santos</creatorcontrib><creatorcontrib>Mesquita-Ferrari, Raquel Agnelli</creatorcontrib><creatorcontrib>Cunha, Regiane Stafim</creatorcontrib><creatorcontrib>Stinghen, Andréa Emilia Marques</creatorcontrib><creatorcontrib>Dalboni, Maria Aparecida</creatorcontrib><creatorcontrib>Barreto, Fellype Carvalho</creatorcontrib><title>Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts</title><title>Archives of medical research</title><addtitle>Arch Med Res</addtitle><description><![CDATA[Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia.
Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry.
Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment.
These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.
Myoblast viability was significantly reduced by IS236 in a time-dependent pattern (p <0.05; 84.4%, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48 h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72 h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation, at any IS concentration tested or time-point experiment. These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia. [Display omitted]]]></description><subject>Chronic kidney disease</subject><subject>Indoxyl sulfate</subject><subject>Sarcopenia</subject><issn>0188-4409</issn><issn>1873-5487</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOwzAURC0EoqXwBwh5ySbBryTOBglVPCoVsShdW45jI1dpHGwH0b_HVdstK1_JM3fmHgBuMcoxwuXDJpdebXWbE4TrHJMcEXQGpphXNCsYr87BFGHOM8ZQPQFXIWwQQpyV1SWYUIJ4iVExBatF37rfXQdXY2dk1HDu-uhtM0YdYHRw7fXWKrhKWW7QvZWw2cHkGZXtv-DT4Ibogg3Q9vB955pOhhiuwYWRXdA3x3cG1i_Pn_O3bPnxupg_LTPFCI8ZLZipjUy161rRihheYC5NJesGUyobJIvKSFrqNDJkKEvdGWtbJoua1RWjM3B_2Dt49z3qEMXWBqW7TvbajUEQWhJUsZIUScoOUuVdCF4bMXi7lX4nMBJ7nGIjDjjFHqfARKReyXZ3TBib_d_JdOKXBI8HgU53_ljtRVBW90q31msVRevs_wl_rAyHqQ</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Rodrigues, Gabriela Gomes Cardoso</creator><creator>Dellê, Humberto</creator><creator>Brito, Rodrigo Barbosa Oliveira</creator><creator>Cardoso, Vinícius Oliveira</creator><creator>Fernandes, Kristianne Porta Santos</creator><creator>Mesquita-Ferrari, Raquel Agnelli</creator><creator>Cunha, Regiane Stafim</creator><creator>Stinghen, Andréa Emilia Marques</creator><creator>Dalboni, Maria Aparecida</creator><creator>Barreto, Fellype Carvalho</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202001</creationdate><title>Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts</title><author>Rodrigues, Gabriela Gomes Cardoso ; Dellê, Humberto ; Brito, Rodrigo Barbosa Oliveira ; Cardoso, Vinícius Oliveira ; Fernandes, Kristianne Porta Santos ; Mesquita-Ferrari, Raquel Agnelli ; Cunha, Regiane Stafim ; Stinghen, Andréa Emilia Marques ; Dalboni, Maria Aparecida ; Barreto, Fellype Carvalho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c428t-354f9fa02099c372f8518af7a9b133ab0a57fa36eab040f3446744dd4a5949743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Chronic kidney disease</topic><topic>Indoxyl sulfate</topic><topic>Sarcopenia</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodrigues, Gabriela Gomes Cardoso</creatorcontrib><creatorcontrib>Dellê, Humberto</creatorcontrib><creatorcontrib>Brito, Rodrigo Barbosa Oliveira</creatorcontrib><creatorcontrib>Cardoso, Vinícius Oliveira</creatorcontrib><creatorcontrib>Fernandes, Kristianne Porta Santos</creatorcontrib><creatorcontrib>Mesquita-Ferrari, Raquel Agnelli</creatorcontrib><creatorcontrib>Cunha, Regiane Stafim</creatorcontrib><creatorcontrib>Stinghen, Andréa Emilia Marques</creatorcontrib><creatorcontrib>Dalboni, Maria Aparecida</creatorcontrib><creatorcontrib>Barreto, Fellype Carvalho</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Archives of medical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodrigues, Gabriela Gomes Cardoso</au><au>Dellê, Humberto</au><au>Brito, Rodrigo Barbosa Oliveira</au><au>Cardoso, Vinícius Oliveira</au><au>Fernandes, Kristianne Porta Santos</au><au>Mesquita-Ferrari, Raquel Agnelli</au><au>Cunha, Regiane Stafim</au><au>Stinghen, Andréa Emilia Marques</au><au>Dalboni, Maria Aparecida</au><au>Barreto, Fellype Carvalho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts</atitle><jtitle>Archives of medical research</jtitle><addtitle>Arch Med Res</addtitle><date>2020-01</date><risdate>2020</risdate><volume>51</volume><issue>1</issue><spage>21</spage><epage>29</epage><pages>21-29</pages><issn>0188-4409</issn><eissn>1873-5487</eissn><abstract><![CDATA[Uremic sarcopenia is a complication of chronic kidney disease, particularly in its later stages, which leads to musculoskeletal disability. Uremic toxins have been linked to the pathogenesis of several manifestations of uremic syndrome. We sought to investigate whether indoxyl sulphate (IS), a protein-bound uremic toxin, is implicated in the development of uremic sarcopenia.
Myoblasts were exposed to IS at normal (0.6 mg/L, IS0.6), uremic (53 mg/L, IS53) or maximum uremic (236 mg/L, IS236) concentrations for 24, 48 and 72 h. Cell viability was evaluated by MTT assay and by 7-aminoactinomycin D staining. ROS generation and apoptosis were evaluated by flow cytometry. MyoD and myogenin mRNA expression was evaluated by qRT-PCR and myosin heavy chain expression by immunocytochemistry.
Myoblast viability was reduced by IS236 in a time-dependent pattern (p <0.05; 84.4, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation at any IS concentration tested or time-point experiment.
These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia.
Myoblast viability was significantly reduced by IS236 in a time-dependent pattern (p <0.05; 84.4%, 68.0, and 63.6%). ROS production was significantly higher (p <0.05) in cells exposed to IS53 and IS236 compared to control (untreated cells). The apoptosis rate was significantly higher in cells treated with IS53 and IS236 than in control after 48 h (p <0.05; 4.7 ± 0.1% and 4.6 ± 0.3% vs. 3.1 ± 0.1%, respectively) and 72 h (p <0.05; 9.6 ± 1.1% and 10.4 ± 0.3% vs. 3.1 ± 0.7%, respectively). No effect was observed on MyoD, myogenin, myosin heavy chain expression, and markers of myoblast differentiation, at any IS concentration tested or time-point experiment. These data indicate that IS has direct toxic effects on myoblast by decreasing its viability and increasing cell apoptosis. IS may be a potential target for treating uremic sarcopenia. [Display omitted]]]></abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>32086105</pmid><doi>10.1016/j.arcmed.2019.12.020</doi><tpages>9</tpages></addata></record> |
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| subjects | Chronic kidney disease Indoxyl sulfate Sarcopenia |
| title | Indoxyl Sulfate Contributes to Uremic Sarcopenia by Inducing Apoptosis in Myoblasts |
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