Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line
Besides their prominent function in cellular energy metabolism, the central role of mitochondria has been focused on control of cellular death in last decades. The mitochondrial permeability transition pore (PTP) is involved in the intrinsic pathway of apoptosis via the release of cytochrome c into...
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| description | Besides their prominent function in cellular energy metabolism, the central role of mitochondria has been focused on control of cellular death in last decades. The mitochondrial permeability transition pore (PTP) is involved in the intrinsic pathway of apoptosis via the release of cytochrome
c into cytosol. Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome
c release. The modulation of PTP is still unknown, but calcium is certainly the most important known inducer. In the present study, the preventive effects of metformin on gentamicin ototoxicity were investigated through the changes of intracellular calcium concentrations using calcium imaging in HEI-OC1 cells. Calcium imaging traced the changes of intracellular calcium concentration after the application of 50 mM of gentamicin in both 100 uM of metformin pretreated group and non-pretreated group. These calcium reactions were compared and analyzed with the results of cell viability test, Hoechst staining, intracellular reactive oxygen species level and expression of caspase-3, and poly-ADP-ribose polymerase (PARP). Continuous increase of intracellular calcium concentration (increase of 380/340 ratio) occurred after application of 50 mM of gentamicin. However, there was no change of intracellular calcium concentration in 100 uM metformin pretreated group. Cell viability was significantly higher in 100 uM metformin pretreated group and also, metformin pretreated HEI-OC1 cells produced less ROS that gentamicin alone treated group. Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP. This study demonstrated that metformin prevented gentamicin induced apoptosis through the calcium modulating and ROS reducing anti-apoptotic effects.
► We studied the preventive effects of metformin on gentamicin ototoxicity. ► Metformin prevented the increase of intracellular calcium concentration. ► Metformin increased cell viability and reduced ROS production. ► It reduced the expression of cleaved PARP and caspase-3 (the markers of apoptosis). ► Metformin prevented apoptosis through calcium modulating and ROS reducing effects. |
| doi_str_mv | 10.1016/j.heares.2011.09.005 |
| format | Article |
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c into cytosol. Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome
c release. The modulation of PTP is still unknown, but calcium is certainly the most important known inducer. In the present study, the preventive effects of metformin on gentamicin ototoxicity were investigated through the changes of intracellular calcium concentrations using calcium imaging in HEI-OC1 cells. Calcium imaging traced the changes of intracellular calcium concentration after the application of 50 mM of gentamicin in both 100 uM of metformin pretreated group and non-pretreated group. These calcium reactions were compared and analyzed with the results of cell viability test, Hoechst staining, intracellular reactive oxygen species level and expression of caspase-3, and poly-ADP-ribose polymerase (PARP). Continuous increase of intracellular calcium concentration (increase of 380/340 ratio) occurred after application of 50 mM of gentamicin. However, there was no change of intracellular calcium concentration in 100 uM metformin pretreated group. Cell viability was significantly higher in 100 uM metformin pretreated group and also, metformin pretreated HEI-OC1 cells produced less ROS that gentamicin alone treated group. Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP. This study demonstrated that metformin prevented gentamicin induced apoptosis through the calcium modulating and ROS reducing anti-apoptotic effects.
► We studied the preventive effects of metformin on gentamicin ototoxicity. ► Metformin prevented the increase of intracellular calcium concentration. ► Metformin increased cell viability and reduced ROS production. ► It reduced the expression of cleaved PARP and caspase-3 (the markers of apoptosis). ► Metformin prevented apoptosis through calcium modulating and ROS reducing effects.</description><identifier>ISSN: 0378-5955</identifier><identifier>EISSN: 1878-5891</identifier><identifier>DOI: 10.1016/j.heares.2011.09.005</identifier><identifier>PMID: 21979311</identifier><identifier>CODEN: HERED3</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Apoptosis - drug effects ; Biological and medical sciences ; Blotting, Western ; Calcium - metabolism ; Caspase 3 - metabolism ; Cell Line ; Cell Survival - drug effects ; Cytoprotection ; Drug toxicity and drugs side effects treatment ; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology ; Gentamicins - toxicity ; Hypoglycemic Agents - pharmacology ; Medical sciences ; Metformin - pharmacology ; Mice ; Molecular Imaging ; Non tumoral diseases ; Organ of Corti - drug effects ; Organ of Corti - metabolism ; Organ of Corti - pathology ; Otorhinolaryngology. Stomatology ; Pharmacology. Drug treatments ; Poly(ADP-ribose) Polymerases - metabolism ; Reactive Oxygen Species - metabolism ; Toxicity: respiratory system, ent, stomatology</subject><ispartof>Hearing research, 2011-12, Vol.282 (1), p.92-96</ispartof><rights>2011 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c617t-6edb548616b0a14846d51dea280b2efd55d5d2f657349d8af57c3b8b9359d593</citedby><cites>FETCH-LOGICAL-c617t-6edb548616b0a14846d51dea280b2efd55d5d2f657349d8af57c3b8b9359d593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.heares.2011.09.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25289909$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21979311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Hak Hyun</creatorcontrib><creatorcontrib>Chang, Jiwon</creatorcontrib><creatorcontrib>Yang, Ji Yoon</creatorcontrib><creatorcontrib>Choi, June</creatorcontrib><creatorcontrib>Im, Gi Jung</creatorcontrib><creatorcontrib>Chae, Sung Won</creatorcontrib><title>Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line</title><title>Hearing research</title><addtitle>Hear Res</addtitle><description>Besides their prominent function in cellular energy metabolism, the central role of mitochondria has been focused on control of cellular death in last decades. The mitochondrial permeability transition pore (PTP) is involved in the intrinsic pathway of apoptosis via the release of cytochrome
c into cytosol. Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome
c release. The modulation of PTP is still unknown, but calcium is certainly the most important known inducer. In the present study, the preventive effects of metformin on gentamicin ototoxicity were investigated through the changes of intracellular calcium concentrations using calcium imaging in HEI-OC1 cells. Calcium imaging traced the changes of intracellular calcium concentration after the application of 50 mM of gentamicin in both 100 uM of metformin pretreated group and non-pretreated group. These calcium reactions were compared and analyzed with the results of cell viability test, Hoechst staining, intracellular reactive oxygen species level and expression of caspase-3, and poly-ADP-ribose polymerase (PARP). Continuous increase of intracellular calcium concentration (increase of 380/340 ratio) occurred after application of 50 mM of gentamicin. However, there was no change of intracellular calcium concentration in 100 uM metformin pretreated group. Cell viability was significantly higher in 100 uM metformin pretreated group and also, metformin pretreated HEI-OC1 cells produced less ROS that gentamicin alone treated group. Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP. This study demonstrated that metformin prevented gentamicin induced apoptosis through the calcium modulating and ROS reducing anti-apoptotic effects.
► We studied the preventive effects of metformin on gentamicin ototoxicity. ► Metformin prevented the increase of intracellular calcium concentration. ► Metformin increased cell viability and reduced ROS production. ► It reduced the expression of cleaved PARP and caspase-3 (the markers of apoptosis). ► Metformin prevented apoptosis through calcium modulating and ROS reducing effects.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Calcium - metabolism</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Cytoprotection</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology</subject><subject>Gentamicins - toxicity</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Medical sciences</subject><subject>Metformin - pharmacology</subject><subject>Mice</subject><subject>Molecular Imaging</subject><subject>Non tumoral diseases</subject><subject>Organ of Corti - drug effects</subject><subject>Organ of Corti - metabolism</subject><subject>Organ of Corti - pathology</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pharmacology. Drug treatments</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Toxicity: respiratory system, ent, stomatology</subject><issn>0378-5955</issn><issn>1878-5891</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk2LFDEQhoMo7rj6D0RyEU8zptKd7uQiyOIXLOhh7yGdVI81dHfGJL2w_367mVFvOqeE8FTVS-ph7DWIHQho3h92P9ElzDspAHbC7IRQT9gGdKu3Sht4yjaiWu9GqSv2IueDEKCqWj5nVxJMayqADaMfKRb0he6Rpzggjz13U6FArsNCnoc07_mIpY9ppIm7vaMpF77HqbiR_PJEU5g9Bu6O8VhipsxXbg5UYnrgHoeBDzThS_asd0PGV-fzmt19_nR383V7-_3Lt5uPt1vfQFu2DYZO1bqBphMOal03QUFAJ7XoJPZBqaCC7BvVVrUJ2vWq9VWnO1MpE5Sprtm7U9tjir9mzMWOlNcQbsI4Z2tkJYVs2vZCUhm4gBRagNHNZeS6hv-TII2USl6QU-i2XpLWC1mfSJ9izgl7e0w0uvRgQdhVGnuwJ2nsKo0Vxi7SLGVvzgPmbsTwp-i3JQvw9gy47N3QJzd5yn85JbUxYv37DycOl_3eEyabPeG0yEFpccyGSP9O8gjvXuEp</recordid><startdate>20111201</startdate><enddate>20111201</enddate><creator>Jung, Hak Hyun</creator><creator>Chang, Jiwon</creator><creator>Yang, Ji Yoon</creator><creator>Choi, June</creator><creator>Im, Gi Jung</creator><creator>Chae, Sung Won</creator><general>Elsevier B.V</general><general>Elsevier</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>7X8</scope><scope>7TK</scope></search><sort><creationdate>20111201</creationdate><title>Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line</title><author>Jung, Hak Hyun ; Chang, Jiwon ; Yang, Ji Yoon ; Choi, June ; Im, Gi Jung ; Chae, Sung Won</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c617t-6edb548616b0a14846d51dea280b2efd55d5d2f657349d8af57c3b8b9359d593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Calcium - metabolism</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Cytoprotection</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology</topic><topic>Gentamicins - toxicity</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Medical sciences</topic><topic>Metformin - pharmacology</topic><topic>Mice</topic><topic>Molecular Imaging</topic><topic>Non tumoral diseases</topic><topic>Organ of Corti - drug effects</topic><topic>Organ of Corti - metabolism</topic><topic>Organ of Corti - pathology</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>Pharmacology. Drug treatments</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Toxicity: respiratory system, ent, stomatology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jung, Hak Hyun</creatorcontrib><creatorcontrib>Chang, Jiwon</creatorcontrib><creatorcontrib>Yang, Ji Yoon</creatorcontrib><creatorcontrib>Choi, June</creatorcontrib><creatorcontrib>Im, Gi Jung</creatorcontrib><creatorcontrib>Chae, Sung Won</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>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Hearing research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jung, Hak Hyun</au><au>Chang, Jiwon</au><au>Yang, Ji Yoon</au><au>Choi, June</au><au>Im, Gi Jung</au><au>Chae, Sung Won</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line</atitle><jtitle>Hearing research</jtitle><addtitle>Hear Res</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>282</volume><issue>1</issue><spage>92</spage><epage>96</epage><pages>92-96</pages><issn>0378-5955</issn><eissn>1878-5891</eissn><coden>HERED3</coden><abstract>Besides their prominent function in cellular energy metabolism, the central role of mitochondria has been focused on control of cellular death in last decades. The mitochondrial permeability transition pore (PTP) is involved in the intrinsic pathway of apoptosis via the release of cytochrome
c into cytosol. Metformin, a drug widely used in the treatment of type II diabetes, has recently received attention owing to new findings regarding its effect on apoptosis through mitochondrial permeability transition and cytochrome
c release. The modulation of PTP is still unknown, but calcium is certainly the most important known inducer. In the present study, the preventive effects of metformin on gentamicin ototoxicity were investigated through the changes of intracellular calcium concentrations using calcium imaging in HEI-OC1 cells. Calcium imaging traced the changes of intracellular calcium concentration after the application of 50 mM of gentamicin in both 100 uM of metformin pretreated group and non-pretreated group. These calcium reactions were compared and analyzed with the results of cell viability test, Hoechst staining, intracellular reactive oxygen species level and expression of caspase-3, and poly-ADP-ribose polymerase (PARP). Continuous increase of intracellular calcium concentration (increase of 380/340 ratio) occurred after application of 50 mM of gentamicin. However, there was no change of intracellular calcium concentration in 100 uM metformin pretreated group. Cell viability was significantly higher in 100 uM metformin pretreated group and also, metformin pretreated HEI-OC1 cells produced less ROS that gentamicin alone treated group. Gentamicin increased cleaved PARP and caspase-3, but metformin inhibited the expression of caspase-3 and cleavage of PARP. This study demonstrated that metformin prevented gentamicin induced apoptosis through the calcium modulating and ROS reducing anti-apoptotic effects.
► We studied the preventive effects of metformin on gentamicin ototoxicity. ► Metformin prevented the increase of intracellular calcium concentration. ► Metformin increased cell viability and reduced ROS production. ► It reduced the expression of cleaved PARP and caspase-3 (the markers of apoptosis). ► Metformin prevented apoptosis through calcium modulating and ROS reducing effects.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>21979311</pmid><doi>10.1016/j.heares.2011.09.005</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Apoptosis - drug effects Biological and medical sciences Blotting, Western Calcium - metabolism Caspase 3 - metabolism Cell Line Cell Survival - drug effects Cytoprotection Drug toxicity and drugs side effects treatment Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology Gentamicins - toxicity Hypoglycemic Agents - pharmacology Medical sciences Metformin - pharmacology Mice Molecular Imaging Non tumoral diseases Organ of Corti - drug effects Organ of Corti - metabolism Organ of Corti - pathology Otorhinolaryngology. Stomatology Pharmacology. Drug treatments Poly(ADP-ribose) Polymerases - metabolism Reactive Oxygen Species - metabolism Toxicity: respiratory system, ent, stomatology |
| title | Protective role of antidiabetic drug metformin against gentamicin induced apoptosis in auditory cell line |
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