Sandbox Reserved 508: Difference between revisions
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== Abstract == | == Abstract == | ||
Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain. Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification. There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2. | Heart diseases are the leading cause of death for Americans today. Mitochondria play a crucial role in recovery following ischemia (blood flow restriction) and reperfusion (blood flow return) injury, when a surge of reactive oxygen species (radicals) originating from the mitochondrial electron transport chain causes damage to proteins, lipids and DNA. Uncoupling protein 2 (UCP2), an inner mitochondrial membrane transport protein, is speculated to participate in this protection. The presumed function of UCP2 is carrying protons (H+) into the mitochondrial matrix along a concentration gradient generated by the electron transport chain. Normally, this proton (H+) gradient is used by ATP synthase to phosphorylate ADP to ATP. Under certain conditions, protons (H+) may preferentially be transported through UCP2, creating a detour past ATP synthase (“uncoupling”). Such uncoupling reduces damaging reactive oxygen species whose presence may actually activate UCP2 by residue modification. There are two proposed mechanisms for the transport of protons (H+) into the matrix. One is the direct transport of protons (H+) through UCP2. Alternatively, a fatty acid anion is transported out of the matrix through UCP2, while the protonated fatty acid permeates through the membrane into the matrix. UCP2 must be tightly regulated so it is only active when required, enabling the mitochondria to produce ATP. Understanding transport mechanism and regulation of UCP2 could lead to effective prevention of tissue injury due to heart attack. The Brookfield Central High School SMART Team created a physical model of UCP2 using 3-D modeling printing technology in order to better understand the structure-function relationship of UCP2. | ||
== Data Piece == | |||
[[Image:BCSMART_11-12_Figure_7.JPG|center|375px| | |||
'''FIGURE 7: The Effect of UCP2 on ROS Production''' | |||
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The data above shows the effect of UCP2 on ROS production. The ROS is made visible by DCF fluorescence(dichloro-fluorescein, which fluoresces in the presence of H2O2). ROS species are introduced into neonatal rat cardiac ventricular myocytes by injecting H2O2. | |||
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A. Confocal microscope images of cardiomyocytes’ ROS production | |||
Top row: ROS in myoctes which have been exposed to adenovirus without the UCP2 protein. Increased DCF fluorescence can be seen over time, representing the presence of a significant level of ROS. Bottom row: ROS in a myocytes exposed to an adenovirus producing the UCP2 protein.DCF fluorescence is barely visible, representing little to no ROS presence. | |||
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B. Quantitative representation of the changes in ROS levels corresponding to the fluorescence images in A using time-lapse confocal microscopy. | |||
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The presence of UCP2 greatly reduces ROS levels, limiting damage to cardiac ventricular myocytes.]] | |||
== Figures == | == Figures == | ||
[[Image:BCSMART_11-12_Figure_1.JPG|left|375px|thumb|'''FIGURE 1: Movement of Protons (H+) Across Inner Mitochondrial Membrane'''<br> | [[Image:BCSMART_11-12_Figure_1.JPG|left|375px|thumb|'''FIGURE 1: Movement of Protons (H+) Across Inner Mitochondrial Membrane'''<br> | ||
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The presence of UCP2 greatly reduces ROS levels, limiting damage to cardiac ventricular myocytes.]] | The presence of UCP2 greatly reduces ROS levels, limiting damage to cardiac ventricular myocytes.]] | ||
==References== | ==References== | ||
Berardi, M. J., Shih, W. M., Harrison, S. C., & Chou, J. J. (2011, August 4). Mitochondrial uncoupling protein 2 structure determined by | Berardi, M. J., Shih, W. M., Harrison, S. C., & Chou, J. J. (2011, August 4). Mitochondrial uncoupling protein 2 structure determined by | ||
