Reduced [3H]IP3 binding but unchanged IP3 receptor levels in the rat hippocampus CA1 region following transient global ischemia and tolerance induction

Dahl, Christina; Haug, Lise Sofie; Spilsberg, Bjørn; Johansen, J H; Østvold, Anne Carine; Diemer, Nils Henrik

doi:10.1016/s0197-0186(99)00129-1

Cited by 17 publications

(10 citation statements)

References 53 publications

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“…This idea is consistent with the conclusion of a recent study that showed that ischemia insults (a condition known to generate reactive oxygen species) in certain regions of rat brain caused conformational changes in InsP 3 receptor that led to reduced binding activity without a reduction in receptor protein level (27). However, we also showed that at late time points after alkylation, once the InsP 3 receptor had acquired a nonbinding conformation, a dealkylating treatment with DTT did not rescue any InsP 3 binding activity.…”

Section: Discussionsupporting

confidence: 92%

Thiol-Reactive Agents Biphasically Regulate Inositol 1,4,5-Trisphosphate Binding and Ca2+ Release Activities in Bovine Adrenal Cortex Microsomes*

et al. 2001

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Within all endocrine cells, the inositol 1,4,5-trisphosphate (InsP(3)) receptor plays an important role in regulation of the intracellular Ca(2+) concentration. In the present study we showed that a single short-term treatment with either N-ethylmaleimide (known to decrease InsP(3) receptor activity) or thimerosal (known to increase InsP(3) receptor activity) caused time-dependent biphasic effects on the InsP(3) binding activity of bovine adrenal cortex microsomes. The early potentiating effect of thiol-reactive agents translated into a 2-fold increase in binding affinity and Ca(2+) release efficiency. The late dampening effect of thiol-reactive agents translated into a continuous reduction of the maximal binding capacity of the microsomes with a concomitant decrease in Ca(2+) release efficiency. Under these conditions, Western blot analyses demonstrated that the level of InsP(3) receptor protein was not modified. Sequential treatments with thimerosal and the reducing agent dithiothreitol showed that the InsP(3) receptor can readily oscillate between high and low affinity states that are related to its alkylation state. Our results suggest a common mode of action of thiol-reactive agents on the InsP(3) receptor. These results also support the contention that cellular mechanisms of thiol group modification could play important roles in regulation of the intracellular Ca(2+) concentration.

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Section: Discussionsupporting

confidence: 92%

Thiol-Reactive Agents Biphasically Regulate Inositol 1,4,5-Trisphosphate Binding and Ca2+ Release Activities in Bovine Adrenal Cortex Microsomes*

et al. 2001

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“…Reduced 3 H-IP 3 binding has been observed in cornu ammonis 1 (CA1) hippocampus after unilateral carotid occlusion in gerbils, an effect that was not associated with any decrease in IP 3 R immunoreactivity (Nagata et al, 1994). A more recent study of global ischemia in the rat produced similar results-a reduction in 3 H-IP 3 binding in CA1, but no change in receptor expression (Dahl et al, 2000). The loss of IP 3 binding has also been shown functionally in postischemic brain tissue.…”

Section: Endoplasmic Reticulummentioning

confidence: 74%

Mechanistic Role of Calpains in Postischemic Neurodegeneration

Bevers

Neumar

2007

J Cereb Blood Flow Metab

136

132

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The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular locations are explored. Calpain substrates within synapses, plasma membrane, endoplasmic reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall effect of postischemic calpain activity on calcium regulation and cell death signaling are considered. Finally, potential pathways for calpain-mediated neurodegeneration are outlined in an effort to guide future studies aimed at understanding the downstream pathology of postischemic calpain activity and identifying optimal therapeutic strategies.

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“…Cytosolic Ca 2þ enhances NO synthesis, which inhibits mitochondrial electron transport, and augments the generation of reactive oxygen species (ROS) (Moncada and Erusalimsky 2002 NO and ROS (Bull et al 2008), and by calpain-induced proteolysis (Rardon et al 1990). Calpain causes proteolysis of the IP 3 R resulting in decreased IP 3 binding, suggesting that site-specific cleavage decreases the affinity of the remaining protein species for IP 3 (Nagata et al 1994;Dahl et al 2000). Although this would indicate that calpain prevents Ca 2þ release, it is also possible that the proteolysis simply removes the ligand regulation of the channel and leads to baseline Ca 2þ release from the ER, contributing to Ca 2þ overload (Bevers and Neumar 2008).…”

Section: Salivary Glandsmentioning

confidence: 99%