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Sulindac enhances the killing of cancer cells exposed to oxidative stress
Title
Sulindac enhances the killing of cancer cells exposed to oxidative stress.
Creator
Kreymerman, Alexander, Ayyanathan, Kasirajan, Kesaraju, Shailaja, Dawson-Scully, Ken, Weissbach, Herbert, Graduate College
Date Issued
2011-04-08
PURL
http://purl.flvc.org/fcla/dt/3164545
Subject Headings
Nonsteroidal anti-inflammatory agents, Oxidative stress, Mitochondrial pathology
Format
Document (PDF)
Molecular mechanisms of neuroprotection in the anoxia tolerant freshwater turtle
Title
Molecular mechanisms of neuroprotection in the anoxia tolerant freshwater turtle.
Creator
Kesaraju, Shailaja., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Cardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of...
Show moreCardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of this study is to understand the modulation of key molecular mechanisms involving stress proteins and VEGF that offer neuroprotection and enhance cell survival in the freshwater turtle through anoxia and reoxygenation. In vivo analyses have shown that anoxia induced stress proteins (Hsp72, Hsp60, Grp94, Hsp60, Hsp27, HO-1); modest changes in the Bcl2/Bax ratio and no change in cleaved caspase-3 expression suggesting resistance to neuronal damage. These results were corroborated with immunohistochemical evidence indicating no damage in turtle brain when subjected to the stress of anoxia and A/R. To understand the functional role of Hsp72, siRNA against Hsp72 was utilized to knockdown Hsp72 in vitro (neuronally enriched primary cell cultures established from the turtle). Knockdown cultures were characterized by increased cell death associated with elevated ROS levels. Silencing of Hsp72 knocks down the expression of Bcl2 and increases the expression of Bax, thereby decreasing the Bcl2/Bax ratio. However, there was no increase in cytosolic Cytochrome c or the expression levels of cleaved Caspase-3. Significant increase in AIF was observed in the knockdown cultures that increase through anoxia and reoxygenation, suggesting a caspase independent pathway of cell death., Expression of the master regulator of hypoxia, HIF1 alpha and its target gene, VEGF, were analyzed at the mRNA and protein levels. The results showed no significant increase in HIF-1 alpha levels but anoxia VE GF The levels of stress proteins and VEGF returned to control levels during reoxygenation suggesting robust ROS protection mechanisms through reoxygenation. The present study thereby emphasizes Trachemys scripta as an advantageous model to examine anoxia and reoxygenation survival without major damage to the brain due to it's modulation of molecular mechanisms.
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Date Issued
2008
PURL
http://purl.flvc.org/FAU/165943
Subject Headings
Turtles, Physiology, Anoxemia, Proteins, Chemical modification, Oxygen, Physiological effect, Molecular neurobiology
Format
Document (PDF)
Sulindac Enhances the Killing of Cancer Cells Exposed to Oxidative Stress
Title
Sulindac Enhances the Killing of Cancer Cells Exposed to Oxidative Stress.
Creator
Marchetti, Maria, Resnick, Lionel, Gamliel, Edna, Kesaraju, Shailaja, Weissbach, Herbert, Binninger, David, Bauer, Joseph Alan
Date Issued
2009-06-05
PURL
http://purl.flvc.org/fau/fd/FAUIR000108
Format
Citation
Combination of Sulindac and Dichloroacetate Kills Cancer Cells via Oxidative Damage
Title
Combination of Sulindac and Dichloroacetate Kills Cancer Cells via Oxidative Damage.
Creator
Ayyanathan, Kasirajan, Kesaraju, Shailaja, Dawson-Scully, Ken, Weissbach, Herbert, Bauer, Joseph Alan
Date Issued
2012-07-17
PURL
http://purl.flvc.org/fau/fd/FAUIR000091
Format
Citation
Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α
Title
Pharmacological protection of retinal pigmented epithelial cells by sulindac involves PPAR-α.
Creator
Sur, Arunodoy, Kesaraju, Shailaja, Prentice, Howard, Ayyanathan, Kasirajan, Baronas-Lowell, Diane, Zhu, Danhong, Hinton, David R., Blanks, Janet, Weissbach, Herbert
Date Issued
2014-11-10
PURL
http://purl.flvc.org/fau/flvc_fau_islandoraimporter_10.1073_pnas.1419576111_1631807081
Format
Citation