Journal ArticleDOI
New nuclear functions of the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase, in mammalian cells.
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TLDR
New investigations establish a primary role for GAPDH in a variety of critical nuclear pathways apart from its already recognized role in apoptosis, including its requirement for transcriptional control of histone gene expression, its essential function in nuclear membrane fusion, and its necessity for the recognition of fraudulently incorporated nucleotides in DNA.Abstract:
Recent studies establish that the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), is not simply a classical metabolic protein involved in energy production. Instead, it is a multifunctional protein with defined functions in numerous subcellular processes. New investigations establish a primary role for GAPDH in a variety of critical nuclear pathways apart from its already recognized role in apoptosis. These new roles include its requirement for transcriptional control of histone gene expression, its essential function in nuclear membrane fusion, its necessity for the recognition of fraudulently incorporated nucleotides in DNA, and its mandatory participation in the maintenance of telomere structure. Each of these new functions requires GAPDH association into a series of multienzyme complexes. Although other proteins in those complexes are variable, GAPDH remains the single constant protein in each structure. To undertake these new functions, GAPDH is recruited to the nucleus in S phase or its intracellular distribution is regulated as a function of drug exposure. Other investigations relate a substantial role for nuclear GAPDH in hyperglycemic stress and the development of metabolic syndrome. Considerations of future directions as well as the role of GAPDH post-translational modification as a basis for its multifunctional activities is suggested.read more
Citations
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Journal ArticleDOI
Glycolysis inhibition for anticancer treatment
TL;DR: The increased dependence of cancer cells on glycolytic pathway for ATP generation provides a biochemical basis for the design of therapeutic strategies to preferentially kill cancer cells by pharmacological inhibition of Glycolysis.
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The Warburg effect and its cancer therapeutic implications
TL;DR: A brief summary of the current understanding of the Warburg effect, the underlying mechanisms, and its influence on the development of therapeutic strategies for cancer treatment is provided.
Journal ArticleDOI
Protection against Fatty Liver but Normal Adipogenesis in Mice Lacking Adipose Differentiation-Related Protein
Benny Hung-Junn Chang,Lan Li,Antoni Paul,Susumu Taniguchi,Vijayalakshmi Nannegari,William C. Heird,Lawrence Chan +6 more
TL;DR: The reduction of TG in the cytosol with concomitant accumulation ofTG in the microsome of Adfp−/− cells suggests that ADFP may facilitate the formation of new LDs, which are thought to form from the outer leaflet of the microsomal membrane.
Journal ArticleDOI
On the functional diversity of glyceraldehyde-3-phosphate dehydrogenase: biochemical mechanisms and regulatory control.
TL;DR: Fundamental roles of GAPDH in vivo, dynamic changes in its subcellular localization, and the importance of posttranslational modifications as well as protein:protein interactions as regulatory control mechanisms are demonstrated.
Journal ArticleDOI
Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives.
TL;DR: Alterations associated with oxidative stress offer many potential therapeutic targets making this an area of great interest to the development of safe and effective treatments for diabetic retinopathy.
References
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superoxide production blocks three pathways of hyperglycaemic damage
Takeshi Nishikawa,Diane Edelstein,Xue Liang Du,Sho-ichi Yamagishi,Takeshi Matsumura,Yasufumi Kaneda,Mark A. Yorek,David Beebek,Peter J. Oatesk,Hans-Peter Hammes,Ida Giardino,Michael Brownlee +11 more
TL;DR: This paper showed that hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells and that this increase in reactive oxygen can be prevented by an inhibitor of electron transport chain complex II, an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase.
Journal ArticleDOI
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Takeshi Nishikawa,Diane Edelstein,Xue Liang Du,Sho-ichi Yamagishi,Takeshi Matsumura,Yasufumi Kaneda,Mark A. Yorek,David A. Beebe,Peter J. Oates,Hans-Peter Hammes,Ida Giardino,Michael Brownlee +11 more
TL;DR: This work shows that hyperglycaemia increases the production of reactive oxygen species inside cultured bovine aortic endothelial cells and is prevented by an inhibitor of electron transport chain complex II, by an uncoupler of oxidative phosphorylation, by uncoupling protein-1 and by manganese superoxide dismutase.
Journal ArticleDOI
Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome
Maria Eriksson,W. Ted Brown,Leslie B. Gordon,Leslie B. Gordon,Michael W. Glynn,Joel Singer,Laura J. Scott,Michael R. Erdos,Christiane M. Robbins,Tracy Moses,Peter Berglund,Amalia Dutra,Evgenia Pak,Sandra G. Durkin,Antonei B. Csoka,Michael Boehnke,Thomas W. Glover,Francis S. Collins +17 more
TL;DR: Evidence of mutations in lamin A (LMNA) as the cause of Hutchinson–Gilford progeria syndrome is presented, and the discovery of the molecular basis of this disease may shed light on the general phenomenon of human ageing.
Journal ArticleDOI
Lamin a truncation in hutchinson-gilford progeria
Annachiara De Sandre-Giovannoli,Rafaëlle Bernard,Pierre Cau,Claire Navarro,Jeanne Amiel,Irène Boccaccio,Stanislas Lyonnet,Colin L. Stewart,Arnold Munnich,Martine Le Merrer,Nicolas Lévy +10 more
TL;DR: HGPS is an exceedingly rare but typical progeria, clinically characterized by postnatal growth retardation, midface hypoplasia, micrognathia, premature atherosclerosis, absence of subcutaneous fat, and others.
Journal ArticleDOI
Pathophysiology of insulin resistance in human disease
TL;DR: It is concluded that insulin resistance and its associated abnormalities are of utmost importance in the pathogenesis of NIDDM, hypertension, and coronary heart disease.