The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform

Kazumichi Furuyama - One of the best experts on this subject based on the ideXlab platform.

  • Hereditary Sideroblastic Anemia: pathophysiology and gene mutations
    International Journal of Hematology, 2010
    Co-Authors: Hideo Harigae, Kazumichi Furuyama
    Abstract:

    Sideroblastic Anemia is characterized by Anemia with the emergence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroblasts characterized by iron accumulation in perinuclear mitochondria due to impaired iron utilization. There are two forms of Sideroblastic Anemia, i.e., inherited and acquired Sideroblastic Anemia. Inherited Sideroblastic Anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron–sulfur (Fe–S) cluster biogenesis, or Fe–S cluster transport, and mitochondrial metabolism. The most common inherited Sideroblastic Anemia is X-linked Sideroblastic Anemia (XLSA) caused by mutations of the erythroid-specific δ-aminolevulinate synthase gene ( ALAS2 ), which is the first enzyme of heme biosynthesis in erythroid cells. Sideroblastic Anemia due to SLC25A38 gene mutations, which is a mitochondrial transporter, is the next most common inherited Sideroblastic Anemia. Other forms of inherited Sideroblastic Anemia are very rare, and accompanied by impaired function of organs other than hematopoietic tissue, such as the nervous system, muscle, or exocrine glands due to impaired mitochondrial metabolism. Moreover, there are still significant numbers of cases with genetically undefined inherited Sideroblastic Anemia. Molecular analysis of these cases will contribute not only to the development of effective treatment, but also to the understanding of mitochondrial iron metabolism.

  • Multiple mechanisms for Hereditary Sideroblastic Anemia
    Cellular and molecular biology (Noisy-le-Grand France), 2002
    Co-Authors: Kazumichi Furuyama, Shigeru Sassa
    Abstract:

    Hereditary Sideroblastic Anemia (HSA) is a heterogeneous group of inherited anemic disorders which is characterized by the presence of ringed sideroblasts in the bone marrow, microcytic hypochromic Anemia and typically its X-linked inheritance in patients. It has been shown that a deficiency of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) activity is responsible for pyridoxine-responsive HSA in many patients, however, the pathogenesis of other types of HSA remains still unknown. In this article, recent evidence suggesting multiple causes for HSA is summarized and discussed.

S. Levi - One of the best experts on this subject based on the ideXlab platform.

  • Over-expression of mitochondrial ferritin affects the JAK2/STAT5 pathway in K562 cells and causes mitochondrial iron accumulation.
    2011
    Co-Authors: P. Santambrogio, B.g. Erba, A. Campanella, A. Cozzi, V. Causarano, L. Cremonesi, A. Gallì, M G. Della Porta, R. Invernizzi, S. Levi
    Abstract:

    Mitochondrial ferritin is a nuclear encoded iron-storage protein localized in mitochondria. It has anti-oxidant properties related to its ferroxidase activity, and it is able to sequester iron avidly into the organelle. The protein has a tissue-specific pattern of expression and is also highly expressed in sideroblasts of patients affected by Hereditary Sideroblastic Anemia and by refractory Anemia with ringed sideroblasts. The present study examined whether mitochondrial ferritin has a role in the pathogenesis of these diseases.We analyzed the effect of mitochondrial ferritin over-expression on the JAK2/STAT5 pathway, on iron metabolism and on heme synthesis in erythroleukemic cell lines. Furthermore its effect on apoptosis was evaluated on human erythroid progenitors.Data revealed that a high level of mitochondrial ferritin reduced reactive oxygen species and Stat5 phosphorylation while promoting mitochondrial iron loading and cytosolic iron starvation. The decline of Stat5 phosphorylation induced a decrease of the level of anti-apoptotic Bcl-xL transcript compared to that in control cells; however, transferrin receptor 1 transcript increased due to the activation of the iron responsive element/iron regulatory protein machinery. Also, high expression of mitochondrial ferritin increased apoptosis, limited heme synthesis and promoted the formation of Perls-positive granules, identified by electron microscopy as iron granules in mitochondria.Our results provide evidence suggesting that Stat5-dependent transcriptional regulation is displaced by strong cytosolic iron starvation status induced by mitochondrial ferritin. The protein interferes with JAK2/STAT5 pathways and with the mechanism of mitochondrial iron accumulation

Shigeru Sassa - One of the best experts on this subject based on the ideXlab platform.

  • Multiple mechanisms for Hereditary Sideroblastic Anemia
    Cellular and molecular biology (Noisy-le-Grand France), 2002
    Co-Authors: Kazumichi Furuyama, Shigeru Sassa
    Abstract:

    Hereditary Sideroblastic Anemia (HSA) is a heterogeneous group of inherited anemic disorders which is characterized by the presence of ringed sideroblasts in the bone marrow, microcytic hypochromic Anemia and typically its X-linked inheritance in patients. It has been shown that a deficiency of the erythroid-specific delta-aminolevulinate synthase (ALAS-E) activity is responsible for pyridoxine-responsive HSA in many patients, however, the pathogenesis of other types of HSA remains still unknown. In this article, recent evidence suggesting multiple causes for HSA is summarized and discussed.

P. Santambrogio - One of the best experts on this subject based on the ideXlab platform.

  • Over-expression of mitochondrial ferritin affects the JAK2/STAT5 pathway in K562 cells and causes mitochondrial iron accumulation.
    2011
    Co-Authors: P. Santambrogio, B.g. Erba, A. Campanella, A. Cozzi, V. Causarano, L. Cremonesi, A. Gallì, M G. Della Porta, R. Invernizzi, S. Levi
    Abstract:

    Mitochondrial ferritin is a nuclear encoded iron-storage protein localized in mitochondria. It has anti-oxidant properties related to its ferroxidase activity, and it is able to sequester iron avidly into the organelle. The protein has a tissue-specific pattern of expression and is also highly expressed in sideroblasts of patients affected by Hereditary Sideroblastic Anemia and by refractory Anemia with ringed sideroblasts. The present study examined whether mitochondrial ferritin has a role in the pathogenesis of these diseases.We analyzed the effect of mitochondrial ferritin over-expression on the JAK2/STAT5 pathway, on iron metabolism and on heme synthesis in erythroleukemic cell lines. Furthermore its effect on apoptosis was evaluated on human erythroid progenitors.Data revealed that a high level of mitochondrial ferritin reduced reactive oxygen species and Stat5 phosphorylation while promoting mitochondrial iron loading and cytosolic iron starvation. The decline of Stat5 phosphorylation induced a decrease of the level of anti-apoptotic Bcl-xL transcript compared to that in control cells; however, transferrin receptor 1 transcript increased due to the activation of the iron responsive element/iron regulatory protein machinery. Also, high expression of mitochondrial ferritin increased apoptosis, limited heme synthesis and promoted the formation of Perls-positive granules, identified by electron microscopy as iron granules in mitochondria.Our results provide evidence suggesting that Stat5-dependent transcriptional regulation is displaced by strong cytosolic iron starvation status induced by mitochondrial ferritin. The protein interferes with JAK2/STAT5 pathways and with the mechanism of mitochondrial iron accumulation

Hideo Harigae - One of the best experts on this subject based on the ideXlab platform.

  • Hereditary Sideroblastic Anemia: pathophysiology and gene mutations
    International Journal of Hematology, 2010
    Co-Authors: Hideo Harigae, Kazumichi Furuyama
    Abstract:

    Sideroblastic Anemia is characterized by Anemia with the emergence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroblasts characterized by iron accumulation in perinuclear mitochondria due to impaired iron utilization. There are two forms of Sideroblastic Anemia, i.e., inherited and acquired Sideroblastic Anemia. Inherited Sideroblastic Anemia is a rare and heterogeneous disease caused by mutations of genes involved in heme biosynthesis, iron–sulfur (Fe–S) cluster biogenesis, or Fe–S cluster transport, and mitochondrial metabolism. The most common inherited Sideroblastic Anemia is X-linked Sideroblastic Anemia (XLSA) caused by mutations of the erythroid-specific δ-aminolevulinate synthase gene ( ALAS2 ), which is the first enzyme of heme biosynthesis in erythroid cells. Sideroblastic Anemia due to SLC25A38 gene mutations, which is a mitochondrial transporter, is the next most common inherited Sideroblastic Anemia. Other forms of inherited Sideroblastic Anemia are very rare, and accompanied by impaired function of organs other than hematopoietic tissue, such as the nervous system, muscle, or exocrine glands due to impaired mitochondrial metabolism. Moreover, there are still significant numbers of cases with genetically undefined inherited Sideroblastic Anemia. Molecular analysis of these cases will contribute not only to the development of effective treatment, but also to the understanding of mitochondrial iron metabolism.