High affinity Ca2+-stimulated Mg2+-dependent ATPase in rat brain synaptosomes, synaptic membranes, and microsomes.

Michaelis, Elias K.; Michaelis, Mary L.; Chang, Hsuan H.; Kitos, T.E.

doi:10.1016/s0021-9258(18)32378-0

Cited by 128 publications

(3 citation statements)

References 41 publications

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“…Western-blot data also showed that both the pre-existing The initial change in alternative splice variant expression is not dependent on new protein synthesis. The change in alternative splice variant expression could not be blocked when IMR32 cells were preincubated for 30 min in MEM containing 50 g ml -1 cycloheximide followed by a 6 h pulse of K + depolarization (in the continuous presence of 50 g ml Historically, synaptosomal preparations from mammalian brain have been one of the richest sources of purified PMCA [31][32][33][34]. The discovery of the abundance of the calcium extrusion pump in this location was due in part to a concerted effort by several groups [32,35,36] to identify mechanisms that may modify synapses and their components as a function of use, a phenomenon commonly referred to as synaptic plasticity.…”

Section: Discussionmentioning

confidence: 99%

Change in plasma membrane Ca2+-ATPase splice-variant expression in response to a rise in intracellular Ca2+

Zacharias

Strehler

1996

Current Biology

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Calcium signaling exerts a direct influence on the regulation of alternative splicing. Notably, a calcium-mediated change in the expression of alternatively spliced variants of a calcium regulatory protein was discovered. The change in splicing occurs quickly, is persistent but reversible and leads to a corresponding change in protein expression. The specific nature in which differently spliced protein variants are expressed, and now the fact that their expression can be regulated by distinct intracellular signaling pathways, suggests that the regulation of alternative splicing by physiological stimuli is a widespread regulatory mechanism by which a cell may coordinate its responses to environmental cues.

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Section: Discussionmentioning

confidence: 99%

Change in plasma membrane Ca2+-ATPase splice-variant expression in response to a rise in intracellular Ca2+

Zacharias

Strehler

1996

Current Biology

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“…Ca2+-ATPase and ATP-dependent Ca2+ uptake activities have been identified in plasma membranes from various cell types (Schatzman, 1981;Michaelis et al, 1983;Papazian et al, 1984), sequestration organelles (deMeis & Inesi, 1982;Chan et al, 1984), and mitochondria (Crompton & Carafoli, 1979). A systematic purification and characterization of the membrane subfractions containing these activities has been instrumental in determining their functional significance.…”

mentioning

confidence: 99%

ATP-dependent calcium uptake activity associated with a disk membrane fraction isolated from bovine retinal rod outer segments

Puckett¹,

Aronson²,

Goldin³

1985

Biochemistry

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Ca2+ sequestration and release from disks of rod outer segments may play a critical role in visual transduction. An ATP-dependent Ca2+ uptake activity has been identified in association with purified disks of bovine rod outer segments. A crude preparation of osmotically active disks was obtained from rod outer segments by hypoosmotic shock and subsequent flotation on a 5% Ficoll 400 solution. These "crude" disks were further purified by separation into two distinct components by centrifugation in a linear Ficoll gradient. Disks comprised the major component; at least 60% of the protein was rhodopsin. This fraction also contained a Ca2+ uptake activity stimulated approximately 4-fold by ATP. The initial rate was approximately 0.21 nmol of Ca2+ (mg of protein)-1 min-1. Most of the ATP-dependent accumulation of 45Ca2+ was released by the calcium ionophore A23187. The uptake activity was sensitive to vanadate (Ki approximately 20 microM) and insensitive to the mitochondrial Ca2+ uptake inhibitor ruthenium red (10 microM). The ATP-dependent Ca2+ uptake exhibited Michaelis-Menten activation kinetics with respect to [Ca2+] (Km approximately 6 microM). The osmotic properties of the sealed disk membranes were exploited to determine whether the association of Ca2+ transport activity with the disks was merely coincidental. The sedimentation properties of these disks, upon centrifugation on a second Ficoll linear density gradient, varied with the osmolarity of the gradient solution. In several separate gradient solutions of differing osmotic and ionic strengths, the Ca2+ uptake activity always comigrated with the disks. These results indicate that the ATP-dependent Ca2+ uptake activity was physically associated with sealed native disk membranes. The characteristics of the Ca2+ uptake activity suggest that it may play a major role in the regulation of cytosolic Ca2+ levels in rod cells in vivo.

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“…The PDHK activity in mouse brain mitochondria or SH-SY5Y cell homogenates was the net ATP-dependent suppression of PDH complex (PDHC) activity ( Sheu et al, 1984 ; Butterworth, 1989 ). The brains from mice were removed following decapitation, specific regions were dissected ( Bao et al, 2009 ), and each region homogenized in buffered 0.32 M sucrose/MgSO 4 medium containing protease inhibitors ( Michaelis et al, 1983 ). The homogenates were aliquoted to tubes (25 μL/tube), rapidly frozen in liquid N 2 and stored (−80°C).…”

Section: Methodsmentioning

confidence: 99%

Protection against Aβ-induced neuronal damage by KU-32: PDHK1 inhibition as important target

Pal,

Hui,

Menchen

et al. 2023

Front. Aging Neurosci.

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A feature of most neurodegenerative diseases is the presence of “mis-folded proteins” that form aggregates, suggesting suboptimal activity of neuronal molecular chaperones. Heat shock protein 90 (Hsp90) is the master regulator of cell responses to “proteotoxic” stresses. Some Hsp90 modulators activate cascades leading to upregulation of additional chaperones. Novobiocin is a modulator at the C-terminal ATP-binding site of Hsp90. Of several novobiocin analogs synthesized and tested for protection against amyloid beta (Aβ)-induced neuronal death, “KU-32” was the most potent in protecting primary neurons, but did not increase expression of other chaperones believed to help clear misfolded proteins. However, KU-32 reversed Aβ-induced superoxide formation, activated Complex I of the electron transfer chain in mitochondria, and blocked the Aβ-induced inhibition of Complex I in neuroblastoma cells. A mechanism for these effects of KU-32 on mitochondrial metabolism appeared to be the inhibition of pyruvate dehydrogenase kinase (PDHK), both in isolated brain mitochondria and in SH-SY5Y cells. PDHK inhibition by the classic enzyme inhibitor, dichloroacetate, led to neuroprotection from Aβ25-35-induced cell injury similarly to KU-32. Inhibition of PDHK in neurons would lead to activation of the PDH complex, increased acetyl-CoA generation, stimulation of the tricarboxylic acid cycle and Complex I in the electron transfer chain, and enhanced oxidative phosphorylation. A focus of future studies may be on the potential value of PDHK as a target in AD therapy.

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High affinity Ca2+-stimulated Mg2+-dependent ATPase in rat brain synaptosomes, synaptic membranes, and microsomes.

Cited by 128 publications

References 41 publications

Change in plasma membrane Ca2+-ATPase splice-variant expression in response to a rise in intracellular Ca2+

Change in plasma membrane Ca2+-ATPase splice-variant expression in response to a rise in intracellular Ca2+

ATP-dependent calcium uptake activity associated with a disk membrane fraction isolated from bovine retinal rod outer segments

Protection against Aβ-induced neuronal damage by KU-32: PDHK1 inhibition as important target

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