Substitutions at a rheostat position in human aldolase A cause a shift in the conformational population

2021 ◽  
Author(s):  
Kathryn D. Fenton ◽  
Kathleen M. Meneely ◽  
Tiffany Wu ◽  
Tyler A. Martin ◽  
Liskin Swint‐Kruse ◽  
...  
Keyword(s):  
Conformational Population ◽  
Aldolase A

scholarly journals An opportunistic promoter sharing regulatory sequences with either a muscle-specific or a ubiquitous promoter in the human aldolase A gene.

1993 ◽  
Vol 13 (1) ◽  
pp. 9-17 ◽  
Author(s):  
J P Concordet ◽  
M Salminen ◽  
J Demignon ◽  
C Moch ◽  
P Maire ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Integration Site ◽  
Regulatory Elements ◽  
Regulatory Sequences ◽  
Beta Globin ◽  
Fast Skeletal Muscle ◽  
High Level Expression ◽  
Adult Skeletal Muscle ◽  
High Level ◽  
Aldolase A

The human aldolase A gene is transcribed from three different promoters, pN, pM, and pH, all of which are clustered within a small 1.6-kbp DNA domain. pM, which is highly specific to adult skeletal muscle, lies in between pN and pH, which are ubiquitous but particularly active in heart and skeletal muscle. A ubiquitous enhancer, located just upstream of pH start sites, is necessary for the activity of both pH and pN in transient transfection assays. Using transgenic mice, we studied the sequence controlling the muscle-specific promoter pM and the relations between the three promoters and the ubiquitous enhancer. A 4.3-kbp fragment containing the three promoters and the ubiquitous enhancer showed an expression pattern consistent with that known in humans. In addition, while pH was active in both fast and slow skeletal muscles, pM was active only in fast muscle. pM activity was unaltered by the deletion of a 1.8-kbp region containing the ubiquitous enhancer and the pH promoter, whereas pN remained active only in fast skeletal muscle. These findings suggest that in fast skeletal muscle, a tissue-specific enhancer was acting on both pN and pM, whereas in other tissues, the ubiquitous enhancer was necessary for pN activity. Finally, a 2.6-kbp region containing the ubiquitous enhancer and only the pH promoter was sufficient to bring about high-level expression of pH in cardiac and skeletal muscle. Thus, while pH and pM function independently of each other, pN, remarkably, shares regulatory elements with each of them, depending on the tissue. Importantly, expression of the transgenes was independent of the integration site, as originally described for transgenes containing the beta-globin locus control region.

Inherited Metabolic Myopathy and Hemolysis Due to a Mutation in Aldolase A

1996 ◽  
Vol 334 (17) ◽  
pp. 1100-1105 ◽  
Author(s):  
Joachim Kreuder ◽  
Arndt Borkhardt ◽  
Reinald Repp ◽  
Arnulf Pekrun ◽  
Barbara Göttsche ◽  
...  
Keyword(s):  
Metabolic Myopathy ◽  
Aldolase A

Involvement of aldolase A in X-ray resistance of human HeLa and UVr-1 cells

2008 ◽  
Vol 369 (3) ◽  
pp. 948-952 ◽  
Author(s):  
Jun Lu ◽  
Toshikazu Suzuki ◽  
Mamoru Satoh ◽  
Shiping Chen ◽  
Takeshi Tomonaga ◽  
...  
Keyword(s):  
X Ray ◽  
Aldolase A

scholarly journals Aldolase A deficiency: Report of new cases and literature review

2021 ◽  
Vol 27 ◽  
pp. 100730
Author(s):  
C. Papadopoulos ◽  
M. Svingou ◽  
K. Kekou ◽  
S. Vergnaud ◽  
S. Xirou ◽  
...  
Keyword(s):  
Literature Review ◽  
Aldolase A

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IN CHILDHOOD AND ADOLESCENCE

PEDIATRICS ◽  
1967 ◽  
Vol 39 (5) ◽  
pp. 675-688
Author(s):  
Denis R. Miller ◽  
Robert L. Baehner ◽  
Louis K. Diamond
Keyword(s):  
Fetal Hemoglobin ◽  
Normal Activity ◽  
Glycolytic Enzyme ◽  
Clinical Severity ◽  
Childhood And Adolescence ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Severity Of The Disease ◽  
Increased Activity ◽  
Aldolase A

Two cases of PNH in adolescence and childhood are reported. The first presented at age 7½ years with aplastic anemia and improved after splenectomy performed at age 14. The second, a 15-year-old girl, presented with a Coombs-positive hemolytic anemia and has had a course complicated by multiple peripheral thromboses. The clinical and laboratory manifestations, complications, and certain therapeutic aspects of PNH are discussed. Anticoagulant therapy appears indicated in the presence of multiple thrombotic episodes. Erythrocyte metabolic studies revealed normal glycolysis, ATP stability, and GSH content in the cells of a child with a normal reticulocyte count. Mild elevations of glycolysis, noted in the child with a reticulocytosis, was ascribed to a younger mean red cell population since further elevations found in the "top" reticulocyte-rich layer after centrifugation. Heparin, the anticoagulant used in these studies, had no adverse effect on glycolysis but did inhibit hemolysis and minimize ATP instability when compared to cells suspended in defibrinated serum. Erythrocytes fractionated by centrifugation revealed increased glycolytic enzyme activities of hexokinase, G3PD, PGK, TPI, PK, LDH, G6PD, and 6PGD in the reticulocyte-rich layer. Normal, rather than increased activity of aldolase, a membrane enzyme, may reflect damage to the red cell membrane. PFK, known to be decreased in the erythrocyte of neonates, showed normal activity, but it was lowest in the reticulocyte-rich layer. Fetal hemoglobin was elevated in this layer. AChE deficiency and increased suceptibility to hydrogen perioxide and acid hemolysis confirmed previous reports and were most marked in the young cell layer. The level of increased glycolytic rates and enzyme activity, AChE deficiency, acid hemolysis and peroxide hemolysis were related to the clinical severity of the disease.

Interactions between sustained contractile activity and beta-adrenergic receptors in regulation of gene expression in skeletal muscles

1989 ◽  
Vol 256 (3) ◽  
pp. C506-C514 ◽  
Author(s):  
W. E. Kraus ◽  
T. S. Bernard ◽  
R. S. Williams
Keyword(s):  
Electrical Stimulation ◽  
Steady State ◽  
Oxidative Metabolism ◽  
Adrenergic Receptors ◽  
Contractile Activity ◽  
Mitochondrial Enzymes ◽  
Beta Adrenergic Receptors ◽  
Beta Adrenergic ◽  
Induced Changes ◽  
Aldolase A

Continuous electrical stimulation for 10-21 days of the motor nerve innervating the anterior compartment muscles of adult rabbits increased both the density of beta-adrenergic receptors (beta-AR) and tissue concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) by two to threefold. Changes in cAMP and in beta-AR occurred in parallel with stimulation-induced adaptations in the specific activity of mitochondrial enzymes (2- to 6-fold increases) and with changes in steady-state concentrations of mitochondrial RNA, beta-F1ATPase mRNA, and myoglobin mRNA (2- to 11-fold increases). These increases in muscle cAMP, in beta-AR, and in expression of protein and mRNA products of genes encoding proteins of oxidative metabolism occurred even in animals receiving high doses of propranolol during the period of electrical stimulation. In contrast to genes that encode proteins of oxidative metabolism, the direction and the time course of activity-induced changes in expression of the glycolytic enzyme aldolase A appeared to be unrelated to changes in muscle cAMP; suppression of steady-state concentrations of aldolase A mRNA was maximal (20-25% of control) at early time points preceding the maximal rise in cAMP. In addition, administration of propranolol attenuated the suppressive effect of continuous contractile activity on expression of aldolase A, even in the absence of an effect of this drug on cAMP in stimulated muscles. We conclude that activity-induced changes in cAMP, in beta-AR, and in expression of genes that encode proteins important for oxidative metabolism occur as a direct consequence of contractile activity and do not require concomitant stimulation of beta-AR.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of the active gene of aldolase on chromosome 16, and two aldolase A pseudogenes on chromosomes 3 and 10

1988 ◽  
Vol 78 (2) ◽  
pp. 167-174 ◽  
Author(s):  
S. Serero ◽  
P. Maire ◽  
Nguyen Van Cong ◽  
O. Cohen-Haguenauer ◽  
M. S. Gross ◽  
...  
Keyword(s):  
Chromosome 16 ◽  
Active Gene ◽  
Aldolase A

scholarly journals A combination of MEF3 and NFI proteins activates transcription in a subset of fast-twitch muscles.

1997 ◽  
Vol 17 (2) ◽  
pp. 656-666 ◽  
Author(s):  
F Spitz ◽  
M Salminen ◽  
J Demignon ◽  
A Kahn ◽  
D Daegelen ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Specific Expression ◽  
Transgenic Lines ◽  
Slow Twitch ◽  
Myogenic Factors ◽  
Fast Twitch ◽  
Restricted Pattern ◽  
Aldolase A ◽  
Drive Reporter Gene Expression

The human aldolase A pM promoter is active in fast-twitch muscles. To understand the role of the different transcription factors which bind to this promoter and determine which ones are responsible for its restricted pattern of expression, we analyzed several transgenic lines harboring different combinations of pM regulatory elements. We show that muscle-specific expression can be achieved without any binding sites for the myogenic factors MyoD and MEF2 and that a 64-bp fragment comprising a MEF3 motif and an NFI binding site is sufficient to drive reporter gene expression in some but, interestingly, not all fast-twitch muscles. A result related to this pattern of expression is that some isoforms of NFI proteins accumulate differentially in fast- and slow-twitch muscles and in distinct fast-twitch muscles. We propose that these isoforms of NFI proteins might provide a molecular basis for skeletal muscle diversity.

Myotube-specific Activity of the Human Aldolase A M-promoter Requires an Overlapping Binding Site For NF1 and MEF2 Factors in Addition to a Binding Site (M1) For Unknown Proteins

1995 ◽  
Vol 253 (1) ◽  
pp. 17-31 ◽  
Author(s):  
Marjo Salminen ◽  
François Spitz ◽  
Marc Y. Fiszman ◽  
Josiane Demignon ◽  
Axel Kahn ◽  
...  
Keyword(s):  
Binding Site ◽  
Specific Activity ◽  
Aldolase A
Sign in / Sign up

Export Citation Format

Share Document