User:Sarah Abdalla/Thioredoxin Reductase: Difference between revisions

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[[Image:Thioredoxin Reductase Mechanism.JPG]]

===Role of Mitochondrial TR in Cardiovascular Development and Cancer===

[[Image:WT and knockout TR embryos.JPG]]

[[Image:WT and knockout TR embryos.JPG |thumb]]

TRs are highly important for control of apoptosis, antioxidant defense, and also have multifaceted roles in cells including implications in cancer. During development, mitochondrial TR is highly expressed in the heart and liver, organs involved in high metabolic activity, which further supports the crucial role of TR in the control of intracellular reactive oxidative species. Studies on mouse embryo have shown that deletion/knockout of mitochondrial TR leads to death at embryonic day 13. The embryos were found to be significantly anemic and smaller than their WT counterparts and showed increased apoptosis in the liver. Also, the ventricular heart walls were thinner and cardiomyocyte proliferation was decreased. The phenotype observed in the TR knockout mice has been observed in Keshan disease, which is a selenium deficiency disease that affects heart function. Knowledge of this disease was the first indication that selenium is essential for heart function. In this same study, hematopoietic colonies were also found to be significantly reduced suggesting their dependence on TR. These results indicate that TR plays a significant role in hematopoiesis development and heart function

The TR system also appears to be involved in separate aspects within the hallmark of cancer. Knockout mice that lack both the mitochondrial and cytosolic forms of thioredoxin and TR die early during embryogenesis, emphasizing the importance of the thioredoxin system. The involvement of TR in antioxidant defense aids in the elimination of carcinogenic oxidants and in the repair of oxidized proteins. Similarly, the reduction of selenite by TR to selenide decreases oxidative stress and may contribute to certain therapeutic effects. TR is a target for existing chemotherapy drugs given its wide substrate specificity and likely involvement in ameliorating cancer during early stages. TR has also been found to be upregulated in some cancers because it provides reducing equivalents for ribonucleotide reductase thereby functioning in the synthesis of deoxyribonucleotides for DNA synetheis.

@@ Line 15: / Line 15: @@
 [[Image:Thioredoxin Reductase Mechanism.JPG]]
 ===Role of Mitochondrial TR in Cardiovascular Development and Cancer===
-[[Image:WT and knockout TR embryos.JPG]]
+[[Image:WT and knockout TR embryos.JPG |thumb]]
 TRs are highly important for control of apoptosis, antioxidant defense, and also have multifaceted roles in cells including implications in cancer.  During development, mitochondrial TR is highly expressed in the heart and liver, organs involved in high metabolic activity, which further supports the crucial role of TR in the control of intracellular reactive oxidative species.  Studies on mouse embryo have shown that deletion/knockout of mitochondrial TR leads to death at embryonic day 13.  The embryos were found to be significantly anemic and smaller than their WT counterparts and showed increased apoptosis in the liver. Also, the ventricular heart walls were thinner and cardiomyocyte proliferation was decreased.  The phenotype observed in the TR knockout mice has been observed in Keshan disease, which is a selenium deficiency disease that affects heart function.  Knowledge of this disease was the first indication that selenium is essential for heart function. In this same study, hematopoietic colonies were also found to be significantly reduced suggesting their dependence on TR.   These results indicate that TR plays a significant role in hematopoiesis development and heart function
 The TR system also appears to be involved in separate aspects within the hallmark of cancer.  Knockout mice that lack both the mitochondrial and cytosolic forms of thioredoxin and TR die early during embryogenesis, emphasizing the importance of the thioredoxin system. The involvement of TR in antioxidant defense aids in the elimination of carcinogenic oxidants and in the repair of oxidized proteins. Similarly, the reduction of selenite by TR to selenide decreases oxidative stress and may contribute to certain therapeutic effects. TR is a target for existing chemotherapy drugs given its wide substrate specificity and likely involvement in ameliorating cancer during early stages. TR has also been found to be upregulated in some cancers because it provides reducing equivalents for ribonucleotide reductase thereby functioning in the synthesis of deoxyribonucleotides for DNA synetheis.