Interaction of Zn2+, and Cu2+, Ions with glyceraldehyde-3-phosphate dehydrogenase from bovine heart and rabbit muscle

Krotkiewska, Bożena; Banaś, Teresa

doi:10.1016/0020-711x(92)90078-f

Cited by 59 publications

(36 citation statements)

References 11 publications

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“…Two other sites include several conserved amino acid residues (specifically, Asp-47, His-50, Asp-186 and Glu-314), and therefore are found in all GAPDHs. These three sites per subunit is consistent with the observation of 10 Zn 2+ bound per GAPDH [64]. The fourth site proposed by Mounaji and coworkers [63] is species-specific and even different between Xenopus laevis and Pleurodeles waltl.…”

Section: Factors Affecting Oligomerizationsupporting

confidence: 81%

Dynamic Oligomeric Properties

Seidler

2012

GAPDH: Biological Properties and Diversity

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This chapter provides a foundation for further research into the relationship between dynamic oligomeric properties and functional diversity. The structural basis that underlies the conformational sub-states of the GAPDH oligomer is discussed. The issue of protein stability is given a thorough analysis, since it is well-established that the primary strategy for protein oligomerization is to stabilize conformation. Several factors that affect oligomerization are described, including chemical modification by synthetic reagents. The effects of native substrates and coenzymes are also discussed. The curious feature of chloride ions having a de-stabilizing effect on native GAPDH structure is described. Additionally, the role of adenine dinucleotides in tetramer-dimer equilibrium dynamics is suggested to be a major part of the physiological regulation of GAPDH structure and function. This chapter also contends that a vast amount of useful information can come from comparative analyses of diverse species, particularly regarding protein stability and subunit-subunit interaction. Lastly, the concept of domain exchange is introduced as a means of understanding the stabilization of dynamic oligomers, suggesting that inter-subunit contacts may also be a way of masking docking sites to other proteins.

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Section: Factors Affecting Oligomerizationsupporting

confidence: 81%

Dynamic Oligomeric Properties

Seidler

2012

GAPDH: Biological Properties and Diversity

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“…Exposure to zinc may induce energetic stress via inhibition of glycolytic enzymes (Ikeda et al, 1980;Krotkiewska and Banas, 1992;Kukimoto et al, 1996), because the resultant cell death can be attenuated by addition of 3 mM niacinamide (Sheline et al, 2000). Similarly, we found that niacinamide provides significant protection against DTDP toxicity.…”

Section: Discussionsupporting

confidence: 60%

p38 Activation Is Required Upstream of Potassium Current Enhancement and Caspase Cleavage in Thiol Oxidant-Induced Neuronal Apoptosis

et al. 2001

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Oxidant-induced neuronal apoptosis has been shown to involve potassium and zinc dysregulation, energetic dysfunction, activation of stress-related kinases, and caspase cleavage. The temporal ordering and interdependence of these events was investigated in primary neuronal cultures exposed to the sulfhydryl oxidizing agent 2,2Ј-dithiodipyridine (DTDP), a compound that induces the intracellular release of zinc. We previously observed that tetraethylammonium (TEA), high extracellular potassium, or cysteine protease inhibitors block apoptosis induced by DTDP. We now report that both p38 and extracellular signal-regulated kinase phosphorylation are evident in neuronal cultures within 2 hr of a brief exposure to 100 M DTDP. However, only p38 inhibition is capable of blocking oxidant-induced toxicity. Cyclohexamide or actinomycin D does not attenuate DTDPinduced cell death, suggesting that posttranslational modification of existing targets, rather than transcriptional activation, is responsible for the deleterious effects of p38. Indeed, an early robust increase in TEA-sensitive potassium channel currents induced by DTDP is attenuated by p38 inhibition but not by caspase inhibition. Moreover, we found that activation of p38 is required for caspase 3 and 9 cleavage, suggesting that potassium currents enhancement is required for caspase activation. Finally, we observed that DTDP toxicity could be blocked with niacinamide or benzamide, inhibitors of poly (ADP-ribose) synthetase. Based on these findings, we conclude that oxidation of sulfhydryl groups on intracellular targets results in intracellular zinc release, p38 phosphorylation, enhancement of potassium currents, caspase cleavage, energetic dysfunction, and translationally independent apoptotic cell death.

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“…More recent evidence suggests that while Zn 2+ apparently translocates into neurons from the extracellular space, it does not come from the histochemically reactive, synaptically released vesicular pool (Lee et al 2000). Lethal [Zn 2+ ] i may also be reached through the oxidation of intracellular zinc binding proteins (Aizenman et al 2000), and several reports indicate that [Zn 2+ ] i is a critical mediator of oxidative damage in whole animal models (Cuajungco and Lees 1998 shows IC 50 s of 400 nM and 1.5 lM for purified GAPDH and phosphofructokinase, respectively (Ikeda et al 1980;Krotkiewska and Bana 1992). Zn 2+ inhibition of GAPDH could be especially deleterious to the cell, given its critical role in the regulation of glycolysis.…”

Section: Interest In Znmentioning

confidence: 99%

Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration

Dineley¹,

Votyakova²,

Reynolds³

2003

Journal of Neurochemistry

310

222

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An increasing body of evidence suggests that high intracellular free zinc promotes neuronal death by inhibiting cellular energy production. A number of targets have been postulated, including complexes of the mitochondrial electron transport chain, components of the tricarboxylic acid cycle, and enzymes of glycolysis. Consequences of cellular zinc overload may include increased cellular reactive oxygen species (ROS) production, loss of mitochondrial membrane potential, and reduced cellular ATP levels. Additionally, zinc toxicity might involve zinc uptake by mitochondria and zinc induction of mitochondrial permeability transition. The present review discusses these processes with special emphasis on their potential involvement in brain injury. Keywords: electron transport chain, glycolysis, metallothionein, permeability transition, reactive oxygen species, tricarboxylic acid cycle. Interest in Zn2+ -mediated brain injury is motivated by evidence implicating Zn 2+ as a neurotoxin in models of stroke, epilepsy, mechanical trauma, and Alzheimer's disease (Choi and Koh 1998). The precise mechanism of cytotoxicity is unknown, but emerging evidence suggests that Zn 2+ kills neurons through the inhibition of ATP synthesis (Weiss et al. 2000). The notion that Zn 2+ affects energy production is admittedly not a new one; indeed, investigators revealed that Zn 2+ impedes mitochondrial function very soon after mitochondria themselves could be properly studied (Hunter and Ford 1955). There has, however, been a resurgence of interest in this general area due to key advances over the last decade. First, a number of seminal reports have allowed a far better understanding of how zinc is regulated under physiological conditions and how disturbances in zinc homeostasis can lead to neuronal injury. Second, neuroscientists have greatly clarified how energy-producing systems such as mitochondria participate in the events leading to neuronal death. Consequently, investigators are now well positioned to explore the impact of zinc on cellular energy production, and how these events may be related to neurodegeneration. This topic is the principal concern of the present review. Initially, we assess data suggesting that zinc interferes with glycolysis, the tricarboxylic acid cycle (TCA), and the mitochondrial electron transport chain. Several related issues also bear consideration, such as mitochondrial generation of reactive oxygen species (ROS) and possible induction of mitochondrial permeability transition (MPT). We then discuss mitochondrial transport of Zn 2+ and possible regulation of metabolism by the metallothionein family of zinc binding proteins. Finally, we examine approaches used in the determination of intracellular free zinc concentrations, which is a critical component of any hypothesis concerning the mechanism of zinc toxicity. More expansive treatments of the neurobiology of Zn 2+ are cited herein. Zinc in the brainZinc is abundant in the brain with levels at 200 ng/mg protein. As suggested by Frederickson (1989), ...

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Interaction of Zn2+, and Cu2+, Ions with glyceraldehyde-3-phosphate dehydrogenase from bovine heart and rabbit muscle

Cited by 59 publications

References 11 publications

Dynamic Oligomeric Properties

Dynamic Oligomeric Properties

p38 Activation Is Required Upstream of Potassium Current Enhancement and Caspase Cleavage in Thiol Oxidant-Induced Neuronal Apoptosis

Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration

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