Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling
To determine the cardiovascular molecular events associated with acute exposure to cocaine, the present study utilized in vivo analysis of left-ventricular heart function in adult rabbits, fluorescence confocal microscopy of fluo-2, rhod-2, (5-(and-6) carboxy 2',7' dichlorodihydrofluores-c...
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| Veröffentlicht in: | Cardiovascular toxicology 2005-01, Vol.5 (4), p.377-390 |
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| creator | Lattanzio, Jr, Frank A Tiangco, David Osgood, Christopher Beebe, Stephen Kerry, Julie Hargrave, Barbara Y |
| description | To determine the cardiovascular molecular events associated with acute exposure to cocaine, the present study utilized in vivo analysis of left-ventricular heart function in adult rabbits, fluorescence confocal microscopy of fluo-2, rhod-2, (5-(and-6) carboxy 2',7' dichlorodihydrofluores-cein diacetate (carboxy-H2DCFDA), and JC-1 in H9C2 cells and gene expression microarray technology for analysis of gene activation in both rabbit ventricular tissue and H9C2 cells. In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1-10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells by 10 microM verapamil, nifedipine, or nadolol inhibited calcium increases, but only 1 mM N-acetylcysteine (NAC) or 1 mM glutathione blocked mitochondrial membrane depolarization. Cocaine induced activation of genes in the rabbit heart and H9C2 cells including angiotensinogen, ADRB1, and c-reactive protein (CRP). In H9C2 cells, NAC pretreatment blocked cocaine-mediated increases in CRP, FAS, FAS ligand, and cytokine receptor-like factor1 (CRLF1) expression. Collectively, these data suggest that acute cocaine administration initiates cellular and genetic changes that, if chronically manifested, could cause cardiac deficits similar to those seen in heart failure and ischemia, such as ventricular dysfunction, cardiac arrhythmias, and cardiac remodeling. |
| doi_str_mv | 10.1385/CT:5:4:377 |
| format | Article |
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In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1-10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells by 10 microM verapamil, nifedipine, or nadolol inhibited calcium increases, but only 1 mM N-acetylcysteine (NAC) or 1 mM glutathione blocked mitochondrial membrane depolarization. Cocaine induced activation of genes in the rabbit heart and H9C2 cells including angiotensinogen, ADRB1, and c-reactive protein (CRP). In H9C2 cells, NAC pretreatment blocked cocaine-mediated increases in CRP, FAS, FAS ligand, and cytokine receptor-like factor1 (CRLF1) expression. Collectively, these data suggest that acute cocaine administration initiates cellular and genetic changes that, if chronically manifested, could cause cardiac deficits similar to those seen in heart failure and ischemia, such as ventricular dysfunction, cardiac arrhythmias, and cardiac remodeling.</description><identifier>ISSN: 1530-7905</identifier><identifier>EISSN: 1530-7905</identifier><identifier>EISSN: 1559-0259</identifier><identifier>DOI: 10.1385/CT:5:4:377</identifier><identifier>PMID: 16382175</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>Acetylcysteine - pharmacology ; Animals ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Cells ; Cocaine ; Cocaine - toxicity ; Dose-Response Relationship, Drug ; Female ; Gene expression ; Gene Expression Regulation - drug effects ; Glutathione - pharmacology ; Heart failure ; Heart Failure - genetics ; Intracellular Membranes - drug effects ; Intracellular Membranes - physiology ; Membrane Potentials - drug effects ; Membrane Potentials - physiology ; Microscopy, Confocal ; Mitochondria - drug effects ; Myocytes, Cardiac - drug effects ; Myocytes, Cardiac - metabolism ; Narcotics - toxicity ; Oligonucleotide Array Sequence Analysis ; Rabbits ; Reactive Oxygen Species - antagonists & inhibitors ; Reactive Oxygen Species - metabolism ; Transcriptional Activation ; Ventricular Function, Left - drug effects ; Ventricular Function, Left - genetics ; Ventricular Remodeling - genetics</subject><ispartof>Cardiovascular toxicology, 2005-01, Vol.5 (4), p.377-390</ispartof><rights>Humana Press Inc. 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-876b4d2eba52e39a1bb8962a8d61122b98c76f97d5745fd27c46e5f1990a884a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16382175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lattanzio, Jr, Frank A</creatorcontrib><creatorcontrib>Tiangco, David</creatorcontrib><creatorcontrib>Osgood, Christopher</creatorcontrib><creatorcontrib>Beebe, Stephen</creatorcontrib><creatorcontrib>Kerry, Julie</creatorcontrib><creatorcontrib>Hargrave, Barbara Y</creatorcontrib><title>Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling</title><title>Cardiovascular toxicology</title><addtitle>Cardiovasc Toxicol</addtitle><description>To determine the cardiovascular molecular events associated with acute exposure to cocaine, the present study utilized in vivo analysis of left-ventricular heart function in adult rabbits, fluorescence confocal microscopy of fluo-2, rhod-2, (5-(and-6) carboxy 2',7' dichlorodihydrofluores-cein diacetate (carboxy-H2DCFDA), and JC-1 in H9C2 cells and gene expression microarray technology for analysis of gene activation in both rabbit ventricular tissue and H9C2 cells. In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1-10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells by 10 microM verapamil, nifedipine, or nadolol inhibited calcium increases, but only 1 mM N-acetylcysteine (NAC) or 1 mM glutathione blocked mitochondrial membrane depolarization. Cocaine induced activation of genes in the rabbit heart and H9C2 cells including angiotensinogen, ADRB1, and c-reactive protein (CRP). In H9C2 cells, NAC pretreatment blocked cocaine-mediated increases in CRP, FAS, FAS ligand, and cytokine receptor-like factor1 (CRLF1) expression. Collectively, these data suggest that acute cocaine administration initiates cellular and genetic changes that, if chronically manifested, could cause cardiac deficits similar to those seen in heart failure and ischemia, such as ventricular dysfunction, cardiac arrhythmias, and cardiac remodeling.</description><subject>Acetylcysteine - pharmacology</subject><subject>Animals</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Cells</subject><subject>Cocaine</subject><subject>Cocaine - toxicity</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Glutathione - pharmacology</subject><subject>Heart failure</subject><subject>Heart Failure - genetics</subject><subject>Intracellular Membranes - drug effects</subject><subject>Intracellular Membranes - physiology</subject><subject>Membrane Potentials - drug effects</subject><subject>Membrane Potentials - physiology</subject><subject>Microscopy, Confocal</subject><subject>Mitochondria - drug effects</subject><subject>Myocytes, Cardiac - drug effects</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Narcotics - toxicity</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Rabbits</subject><subject>Reactive Oxygen Species - antagonists & inhibitors</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Transcriptional Activation</subject><subject>Ventricular Function, Left - drug effects</subject><subject>Ventricular Function, Left - genetics</subject><subject>Ventricular Remodeling - genetics</subject><issn>1530-7905</issn><issn>1530-7905</issn><issn>1559-0259</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpdkc9u3CAQxlGVqkmTXPIAFcqhhyrbAjYG9lZZ_SdF6mV7RmMYZ4lsswW7bfoyedWSzUqJeoER8_u-QfMRcsHZe15p-aHdrOW6XldKvSAnXFZspQyTR8_qY_I651vGhBCNfEWOeVNpwZU8IfdtdBAmpGFyCSFjLtWcwOEwLAMk6mBwYRkpTJ4WwM3hF9L45-4GJ5p36ALmK-pxFwsc_hb5GObotnHyKcDVXrYXwVx6RVROyDm6UB48_R3mLd0ipJn2EIYl4WHQGD0OYbo5Iy97GDKeH-5T8uPzp037dXX9_cu39uP1ylW6nldaNV3tBXYgBVYGeNdp0wjQvuFciM5op5reKC9VLXsvlKsblD03hoHWNVSn5O2j7y7Fnwvm2Y4hPywBJoxLtoJprRujC3j5H3gblzSVv1mtjGS12kPvHiGXYs4Je7tLYYR0ZzmzD5nZdmOlrW3JrMBvDo5LN6J_Qg8hVf8AHUCVBQ</recordid><startdate>20050101</startdate><enddate>20050101</enddate><creator>Lattanzio, Jr, Frank A</creator><creator>Tiangco, David</creator><creator>Osgood, Christopher</creator><creator>Beebe, Stephen</creator><creator>Kerry, Julie</creator><creator>Hargrave, Barbara Y</creator><general>Springer Nature B.V</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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7QP</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20050101</creationdate><title>Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling</title><author>Lattanzio, Jr, Frank A ; Tiangco, David ; Osgood, Christopher ; Beebe, Stephen ; Kerry, Julie ; Hargrave, Barbara Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-876b4d2eba52e39a1bb8962a8d61122b98c76f97d5745fd27c46e5f1990a884a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acetylcysteine - 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In the rabbit, acute cocaine exposure (2 mg/kg) caused left-ventricular dysfunction and 0.1-10 mM cocaine increased cytosolic and mitochondrial calcium activity and mitochondrial membrane depolarization in H9C2 cells. A 3-min pretreatment of H9C2 cells by 10 microM verapamil, nifedipine, or nadolol inhibited calcium increases, but only 1 mM N-acetylcysteine (NAC) or 1 mM glutathione blocked mitochondrial membrane depolarization. Cocaine induced activation of genes in the rabbit heart and H9C2 cells including angiotensinogen, ADRB1, and c-reactive protein (CRP). In H9C2 cells, NAC pretreatment blocked cocaine-mediated increases in CRP, FAS, FAS ligand, and cytokine receptor-like factor1 (CRLF1) expression. 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| ispartof | Cardiovascular toxicology, 2005-01, Vol.5 (4), p.377-390 |
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| subjects | Acetylcysteine - pharmacology Animals Calcium - metabolism Calcium Channel Blockers - pharmacology Cells Cocaine Cocaine - toxicity Dose-Response Relationship, Drug Female Gene expression Gene Expression Regulation - drug effects Glutathione - pharmacology Heart failure Heart Failure - genetics Intracellular Membranes - drug effects Intracellular Membranes - physiology Membrane Potentials - drug effects Membrane Potentials - physiology Microscopy, Confocal Mitochondria - drug effects Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Narcotics - toxicity Oligonucleotide Array Sequence Analysis Rabbits Reactive Oxygen Species - antagonists & inhibitors Reactive Oxygen Species - metabolism Transcriptional Activation Ventricular Function, Left - drug effects Ventricular Function, Left - genetics Ventricular Remodeling - genetics |
| title | Cocaine increases intracellular calcium and reactive oxygen species, depolarizes mitochondria, and activates genes associated with heart failure and remodeling |
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