Reactive oxygen species are implicated in tissue damage in many cardiovascular diseases. The current study was designed to test the hypothesis that exposure to high inspired oxygen concentrations (100%) damages cardiac mitochondria and that a biogenic response is needed for cell survival. The study was done in mice with a transgene (TG) for extracellular superoxide dismutase (EC-SOD) or with the EC-SOD gene knockout (KO). Adult EC-SOD mice and their wild type littermates and EC-SOD KO mice and their wild type littermates were exposed to 100% oxygen for 6 hours and for 72 hours, and the hearts were subsequently removed under deep anesthesia. The mortality rate in KO mice after 72 hours (25%) was significantly higher than wild type littermates (10%) and TG mice (4.2%). In the EC-SOD TG mice, 6 hours of exposure to hyperoxia activated the transcription of nuclear genes important for mitochondrial biogenesis---nuclear respiratory factors (NRF-1 and NRF-2) and their co-regulator PGC-1α---leading to expression of mitochondrial transcription factor A (Tfam), which regulates mitochondrial transcription and replication. Hyperoxia also induced activation of NRF-1 and NRF-2 in EC-SOD KO mice after 6 hours but down-regulated Tfam and PGC1α transcripts. But after 72 hours, mRNA expression for NRF-2, PGC-1α and Tfam increased in these mice.
The protein expression of the pro-survival Protein Kinase B (Akt) was significantly increased by hyperoxia in the TG hearts after 6 hours (ppp
In conclusion, systemic hyperoxia consistently increases mitochondrial biogenesis markers in the mouse heart, most prominently in EC-SOD TG mice, and co-incidentally with increases in Akt, p-Bad and p-GSK-3 R. This suggests that extracellular reactive oxygen products activate mitochondrial biogenesis and the pro-survival pathway in TG mice. Also, hyperoxia decreased the activation of Tfam and PGC-1α transcription after 6 hours and increased it again after 72 hours in KO mice. This was associated with a decrease in expression of Akt, p-Bad and p-GSK-3β and an increase in p38, indicating that either hyperoxia activated mitochondrial biogenesis and pro-survival pathways through p38 or that hyperoxia produced more oxidative damage to the mitochondria in the KO. In the latter case, the increase in p38 may be a signal for activation of apoptotic pathways.
","abstract_html":"<p>Reactive oxygen species are implicated in tissue damage in many cardiovascular diseases. The current study was designed to test the hypothesis that exposure to high inspired oxygen concentrations (100%) damages cardiac mitochondria and that a biogenic response is needed for cell survival. The study was done in mice with a transgene (TG) for extracellular superoxide dismutase (EC-SOD) or with the EC-SOD gene knockout (KO). Adult EC-SOD mice and their wild type littermates and EC-SOD KO mice and their wild type littermates were exposed to 100% oxygen for 6 hours and for 72 hours, and the hearts were subsequently removed under deep anesthesia. The mortality rate in KO mice after 72 hours (25%) was significantly higher than wild type littermates (10%) and TG mice (4.2%). In the EC-SOD TG mice, 6 hours of exposure to hyperoxia activated the transcription of nuclear genes important for mitochondrial biogenesis---nuclear respiratory factors (NRF-1 and NRF-2) and their co-regulator PGC-1α---leading to expression of mitochondrial transcription factor A (Tfam), which regulates mitochondrial transcription and replication. Hyperoxia also induced activation of NRF-1 and NRF-2 in EC-SOD KO mice after 6 hours but down-regulated Tfam and PGC1α transcripts. But after 72 hours, mRNA expression for NRF-2, PGC-1α and Tfam increased in these mice.</p> <p>The protein expression of the pro-survival Protein Kinase B (Akt) was significantly increased by hyperoxia in the TG hearts after 6 hours (<em>p</em>pp</p> <p>In conclusion, systemic hyperoxia consistently increases mitochondrial biogenesis markers in the mouse heart, most prominently in EC-SOD TG mice, and co-incidentally with increases in Akt, p-Bad and p-GSK-3 R. This suggests that extracellular reactive oxygen products activate mitochondrial biogenesis and the pro-survival pathway in TG mice. Also, hyperoxia decreased the activation of Tfam and PGC-1α transcription after 6 hours and increased it again after 72 hours in KO mice. This was associated with a decrease in expression of Akt, p-Bad and p-GSK-3β and an increase in p38, indicating that either hyperoxia activated mitochondrial biogenesis and pro-survival pathways through p38 or that hyperoxia produced more oxidative damage to the mitochondria in the KO. In the latter case, the increase in p38 may be a signal for activation of apoptotic pathways.</p>","abstract_has_math":false,"creators":["Ali, Mervat Elsayed"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Frank J. Castora","Claude A. Piantadosi","Miriam D. Rosenthal","Hajer B. Suliman","Peter F. Blackmore"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-07-01T07:00:00Z","date_published":"2006-07-01T07:00:00Z","updated_at":"2026-07-24T03:34:46Z","subjects":["Cardiomyocytes","Hyperoxia","Superoxide dismutase","Molecular Biology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["9781109910483"],"render_values":[{"text":"9781109910483","href":null,"code":true}]}]},"links":{"outbound_url":"https://digitalcommons.odu.edu/biomedicalsciences_etds/3","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Frank J. Castora","Claude A. Piantadosi","Miriam D. Rosenthal","Hajer B. Suliman","Peter F. Blackmore"]},{"key":"dc:creator","label":"Author","values":["Ali, Mervat Elsayed"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-05-07T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cardiomyocytes","Hyperoxia","Superoxide dismutase","Molecular Biology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["9781109910483","https://digitalcommons.odu.edu/biomedicalsciences_etds/3"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Reactive oxygen species are implicated in tissue damage in many cardiovascular diseases. The current study was designed to test the hypothesis that exposure to high inspired oxygen concentrations (100%) damages cardiac mitochondria and that a biogenic response is needed for cell survival. The study was done in mice with a transgene (TG) for extracellular superoxide dismutase (EC-SOD) or with the EC-SOD gene knockout (KO). Adult EC-SOD mice and their wild type littermates and EC-SOD KO mice and their wild type littermates were exposed to 100% oxygen for 6 hours and for 72 hours, and the hearts were subsequently removed under deep anesthesia. The mortality rate in KO mice after 72 hours (25%) was significantly higher than wild type littermates (10%) and TG mice (4.2%). In the EC-SOD TG mice, 6 hours of exposure to hyperoxia activated the transcription of nuclear genes important for mitochondrial biogenesis---nuclear respiratory factors (NRF-1 and NRF-2) and their co-regulator PGC-1α---leading to expression of mitochondrial transcription factor A (Tfam), which regulates mitochondrial transcription and replication. Hyperoxia also induced activation of NRF-1 and NRF-2 in EC-SOD KO mice after 6 hours but down-regulated Tfam and PGC1α transcripts. But after 72 hours, mRNA expression for NRF-2, PGC-1α and Tfam increased in these mice.
The protein expression of the pro-survival Protein Kinase B (Akt) was significantly increased by hyperoxia in the TG hearts after 6 hours (ppp
In conclusion, systemic hyperoxia consistently increases mitochondrial biogenesis markers in the mouse heart, most prominently in EC-SOD TG mice, and co-incidentally with increases in Akt, p-Bad and p-GSK-3 R. This suggests that extracellular reactive oxygen products activate mitochondrial biogenesis and the pro-survival pathway in TG mice. Also, hyperoxia decreased the activation of Tfam and PGC-1α transcription after 6 hours and increased it again after 72 hours in KO mice. This was associated with a decrease in expression of Akt, p-Bad and p-GSK-3β and an increase in p38, indicating that either hyperoxia activated mitochondrial biogenesis and pro-survival pathways through p38 or that hyperoxia produced more oxidative damage to the mitochondria in the KO. In the latter case, the increase in p38 may be a signal for activation of apoptotic pathways.
"]},{"key":"dc:title","label":"Title","values":["Extracellular Superoxide Dismutase Protects Cardiomyocytes During Hyperoxia"]}]}],"canonical_facts":{"dc:contributor":["Frank J. Castora","Claude A. Piantadosi","Miriam D. Rosenthal","Hajer B. Suliman","Peter F. Blackmore"],"dc:creator":["Ali, Mervat Elsayed"],"dc:date.available":["2019-05-07T07:00:00Z"],"dc:description.abstract":["Reactive oxygen species are implicated in tissue damage in many cardiovascular diseases. The current study was designed to test the hypothesis that exposure to high inspired oxygen concentrations (100%) damages cardiac mitochondria and that a biogenic response is needed for cell survival. The study was done in mice with a transgene (TG) for extracellular superoxide dismutase (EC-SOD) or with the EC-SOD gene knockout (KO). Adult EC-SOD mice and their wild type littermates and EC-SOD KO mice and their wild type littermates were exposed to 100% oxygen for 6 hours and for 72 hours, and the hearts were subsequently removed under deep anesthesia. The mortality rate in KO mice after 72 hours (25%) was significantly higher than wild type littermates (10%) and TG mice (4.2%). In the EC-SOD TG mice, 6 hours of exposure to hyperoxia activated the transcription of nuclear genes important for mitochondrial biogenesis---nuclear respiratory factors (NRF-1 and NRF-2) and their co-regulator PGC-1α---leading to expression of mitochondrial transcription factor A (Tfam), which regulates mitochondrial transcription and replication. Hyperoxia also induced activation of NRF-1 and NRF-2 in EC-SOD KO mice after 6 hours but down-regulated Tfam and PGC1α transcripts. But after 72 hours, mRNA expression for NRF-2, PGC-1α and Tfam increased in these mice.
The protein expression of the pro-survival Protein Kinase B (Akt) was significantly increased by hyperoxia in the TG hearts after 6 hours (ppp
In conclusion, systemic hyperoxia consistently increases mitochondrial biogenesis markers in the mouse heart, most prominently in EC-SOD TG mice, and co-incidentally with increases in Akt, p-Bad and p-GSK-3 R. This suggests that extracellular reactive oxygen products activate mitochondrial biogenesis and the pro-survival pathway in TG mice. Also, hyperoxia decreased the activation of Tfam and PGC-1α transcription after 6 hours and increased it again after 72 hours in KO mice. This was associated with a decrease in expression of Akt, p-Bad and p-GSK-3β and an increase in p38, indicating that either hyperoxia activated mitochondrial biogenesis and pro-survival pathways through p38 or that hyperoxia produced more oxidative damage to the mitochondria in the KO. In the latter case, the increase in p38 may be a signal for activation of apoptotic pathways.
"],"dc:identifier":["9781109910483","https://digitalcommons.odu.edu/biomedicalsciences_etds/3"],"dc:subject":["Cardiomyocytes","Hyperoxia","Superoxide dismutase","Molecular Biology"],"dc:title":["Extracellular Superoxide Dismutase Protects Cardiomyocytes During Hyperoxia"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:34:46Z"}