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Full-Text Articles in Medicine and Health Sciences
The Role Of Mcl-1 In The Heart: Gateway From Life To Death, Xi Wang
The Role Of Mcl-1 In The Heart: Gateway From Life To Death, Xi Wang
Theses and Dissertations (ETD)
MCL-1 is an essential BCL-2 family member that promotes the survival of multiple cellular lineages, but its role in cardiac muscle has remained unclear. Here, we have demonstrated that cardiac-specific ablation of Mcl-1 results in a rapidly fatal, dilated cardiomyopathy preceded by loss of myofibrils and cardiac contractility, abnormal mitochondria ultrastructure, defective mitochondrial respiration, and impaired autophagy. Genetic ablation of both pro-apoptotic effectors (Bax and Bak) could largely rescue the lethality and impaired cardiac function induced by Mcl-1 deletion. However, Mcl-1-, Bax-, and Bak-deficient hearts still revealed mitochondrial ultrastructural abnormalities and displayed deficient mitochondrial respiration, and are hypersensitive to chronic …
Functional Study Of Hemogen Knockout Mouse Model, Peng Gao
Functional Study Of Hemogen Knockout Mouse Model, Peng Gao
Theses and Dissertations (ETD)
Mouse Hemogen (Hemgn) is regarded as a homologue of human Erythroid Differentiation Associated Gene (EDAG). EDAG overexpression has been postulated for association with some leukemia cases. Meanwhile, Hemgn has been found to contribute to Hoxb4 mediated hematopoietic stem cell expansion. Based on these postulations and evidences, a Hemgn knockout mouse model has been generated to study its function in normal and stress hematopoiesis. I confirmed the Hemgn expression in hematopoietic organs including bone marrow and spleen, as well as round spematids in testis. Hemgn is expressed in mouse hematopoietic stem cells and erythroid progenitor cells. Moreover, Hemgn was also found …
Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle
Anti-Apoptotic Mcl-1 Localizes To The Mitochondrial Matrix And Couples Mitochondrial Fusion To Respiration, Rhonda Perciavalle
Theses and Dissertations (ETD)
MCL-1, an anti-apoptotic BCL-2 family member that is essential for the survival of multiple cell lineages, is also among the most highly amplified genes in cancer. Although MCL-1 is known to oppose cell death, precisely how it functions to promote survival of normal and malignant cells is poorly understood. Here, I report that different forms of MCL-1 reside in distinct mitochondrial locations and exhibit separable functions. On the outer mitochondrial membrane, a MCL-1 isoform acts like other anti-apoptotic BCL-2 molecules to antagonize apoptosis, whereas an amino-terminally truncated isoform of MCL-1 that is imported into the mitochondrial matrix is necessary to …