Stimulation by thyroid hormone analogues of red blood cell Ca2+-ATPase activity in vitro. Correlations between hormone structure and biological activity in a human cell system.

This research aimed to evaluate the effect of thyroid hormone deficiency on the erythrocytic system in dogs. Dogs with clinical symptoms of hypothyreosis such as obesity, hyperpigmentation, and lethargy were selected. The dogs demonstrating breed predisposition to hypothyreosis were incorporated in the analysis: Dachshunds, Retrievers, and mixed-breed dogs. A detailed history was taken and clinical, hormonal, biochemical and haematological blood tests were performed. Peripheral blood samples were taken from 53 dogs. Finally, the dogs with the initial T4 (thyroxine) concentration < 1.3 µg/dl and animals demonstrating clinical improvement after a 2-month therapy with levothyroxine at a dose of 10 µg/kg administeredper ostwo times a day were qualified. The animals between 10 months to 13 years of age were divided into two groups: clinically healthy (control group, n = 35) and dogs presenting clinical symptoms of hypothyreosis (experimental group, n = 18). In this research, the broadly described normocytic normochromic non-regenerative anaemia was not diagnosed in dogs with hypothyreosis. However, a positive correlation between T4 and red blood cell indices such as the average mass of haemoglobin per red blood cell, concentration of haemoglobin in a given volume of packed red blood cells as well as a negative correlation with haematocrit value was discovered in the experimental group after the 2-month therapy with levothyroxine. These results point to the influence of thyroid hormones on erythropoiesis. This observation is partially consistent with other studies, which noted the casual link between the changes in red blood cell system and the function of thyroid in dogs and humans.

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The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects inSteel17H Mice

Blood ◽

10.1182/blood.v94.6.1915 ◽

1999 ◽

Vol 94 (6) ◽

pp. 1915-1925 ◽

Cited By ~ 20

Author(s):

Reuben Kapur ◽

Ryan Cooper ◽

Xingli Xiao ◽

Mitchell J. Weiss ◽

Peter Donovan ◽

...

Keyword(s):

Amino Acids ◽

Bone Marrow ◽

Biological Activity ◽

Stem Cell ◽

Blood Cell ◽

Red Blood Cell ◽

Stem Cell Factor ◽

Cytoplasmic Domain

Abstract Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF248) or membrane-associated (MA) (SCF220) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie(Sld) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms.Steel17H (Sl17H) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl17H allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa’s) in the SCF cytoplasmic domain with 28 novel aa’s. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl17H-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl17H mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl17H isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCFX9/D3) SCF in Sl/Sl17H mutants results in a significant improvement in peripheral red blood cell counts in comparison toSl/Sl17H mice.

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Analogue-specific action in vitro of atrial natriuretic factor on human red blood cell Ca2+-ATPase activity.

Hypertension ◽

10.1161/01.hyp.12.4.428 ◽

1988 ◽

Vol 12 (4) ◽

pp. 428-433 ◽

Cited By ~ 3

Author(s):

F B Davis ◽

S D Blas ◽

M M Davis ◽

P J Davis

Keyword(s):

Blood Cell ◽

Atpase Activity ◽

Red Blood Cell ◽

Atrial Natriuretic Factor ◽

Natriuretic Factor ◽

Atrial Natriuretic

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Thyroid Hormone Stimulates Red Blood Cell Ca++-Dependent ATPase Activity Through a “Non-Hormonal” Effect

Frontiers in Thyroidology ◽

10.1007/978-1-4684-5260-0_120 ◽

1986 ◽

pp. 661-666

Author(s):

Giuseppe Costante ◽

Georges Sand ◽

Denis Connart ◽

Daniel Glinoer

Keyword(s):

Thyroid Hormone ◽

Blood Cell ◽

Atpase Activity ◽

Red Blood Cell ◽

Dependent Atpase ◽

Hormonal Effect

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The Presence of Novel Amino Acids in the Cytoplasmic Domain of Stem Cell Factor Results in Hematopoietic Defects inSteel17H Mice

Blood ◽

10.1182/blood.v94.6.1915.418k11_1915_1925 ◽

1999 ◽

Vol 94 (6) ◽

pp. 1915-1925 ◽

Cited By ~ 2

Author(s):

Reuben Kapur ◽

Ryan Cooper ◽

Xingli Xiao ◽

Mitchell J. Weiss ◽

Peter Donovan ◽

...

Keyword(s):

Amino Acids ◽

Bone Marrow ◽

Biological Activity ◽

Stem Cell ◽

Blood Cell ◽

Red Blood Cell ◽

Stem Cell Factor ◽

Cytoplasmic Domain

Stem cell factor (SCF) is expressed as an integral membrane growth factor that may be differentially processed to produce predominantly soluble (S) (SCF248) or membrane-associated (MA) (SCF220) protein. A critical role for membrane presentation of SCF in the hematopoietic microenvironment (HM) has been suggested from the phenotype of the Steel-dickie(Sld) mice, which lack MA SCF, and by studies performed in our laboratory (and by others) using long-term bone marrow cultures and transgenic mice expressing different SCF isoforms.Steel17H (Sl17H) is an SCF mutant that demonstrates melanocyte defects and sterility in males but not in females. The Sl17H allele contains a intronic mutation resulting in the substitution of 36 amino acids (aa’s) in the SCF cytoplasmic domain with 28 novel aa’s. This mutation, which affects virtually the entire cytoplasmic domain of SCF, could be expected to alter membrane SCF presentation. To investigate this possibility, we examined the biochemical and biologic properties of the Sl17H-encoded protein and its impact in vivo and in vitro on hematopoiesis and on c-Kit signaling. We demonstrate that compound heterozygous Sl/Sl17H mice manifest multiple hematopoietic abnormalities in vivo, including red blood cell deficiency, bone marrow hypoplasia, and defective thymopoiesis. In vitro, both S and MA Sl17H isoforms of SCF exhibit reduced cell surface expression on stromal cells and diminished biological activity in comparison to wild-type (wt) SCF isoforms. These alterations in presentation and biological activity are associated with a significant reduction in the proliferation of an SCF-responsive erythroid progenitor cell line and in the activation of phosphatidylinositol 3-Kinase/Akt and mitogen-activated protein-Kinase signaling pathways. In vivo, transgene expression of the membrane-restricted (MR) (SCFX9/D3) SCF in Sl/Sl17H mutants results in a significant improvement in peripheral red blood cell counts in comparison toSl/Sl17H mice.

Download Full-text