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Mitochondrial Protection From Ischemia‐Reoxygenation Injury with Mitochondrial Heat Shock Protein 70 Overexpression
Author(s) -
Hollander John Michael,
Scott Brian T.,
Belke Darrell D.,
Dillmann Wolfgang H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1155-a
Subject(s) - myocyte , mitochondrion , cytosol , heat shock protein , inner mitochondrial membrane , hsp70 , microbiology and biotechnology , biology , mitochondrial matrix , reactive oxygen species , biochemistry , gene , enzyme
The majority of mitochondrial proteins are encoded by nuclear genes and synthesized in the cytosol as preproteins containing a mitochondria import sequence. These preproteins traverse the outer mitochondrial membrane in an unfolded state, and are then translocated through the inner membrane into the matrix via import machinery that includes mitochondrial heat shock protein 70 (mtHsp70). In this study, neonatal rat cardiac myocytes (NCM) were infected with an adenoviral vector expressing mtHsp70 or an empty control (Adv‐) for 48 hours, and submitted to 8 hours of simulated ischemia (hypoxia) followed by 16 hours of reperfusion (reoxygenation). Infection with mtHsp70 virus yielded a large increase in mtHsp70 protein in NCM mitochondria as compared to Adv‐. Cell viability following simulated I/R was greater in mtHsp70 myocytes (P<0.05). Simulated I/R caused a significant increase in reactive oxygen species (ROS) generation in Adv‐infected myocytes (P<0.05), which was not observed in mtHsp70‐infected myocytes. Mitochondrial complex III and IV activities were greater in mtHsp70‐infected myocytes following simulated I/R as compared to Adv‐ (P<0.05 and P<0.01, respectively). Following simulated I/R, ATP content was greater in mtHsp70‐infected cells, as compared to Adv‐ (P<0.05). Further, caspase‐3 activity was lower in mtHsp70‐infected myocytes as compared to Adv‐ after simulated I/R (P<0.05). These results indicate that overexpression of mtHsp70 provides protection to the mitochondria against damage resulting from simulated I/R injury, which may be due in part to a decrease in ROS generation, preserving mitochondrial complex function and ATP formation.