Calpain activation induced by glucose deprivation is mediated by oxidative stress and contributes to neuronal damage

Paramo, Blanca; Montiel, Teresa; Hernández-Espinosa, Diego Rolando; Rivera-Martínez, Marlene; Morán, Julio; Massieu, Lourdes

doi:10.1016/j.biocel.2013.08.013

Cited by 28 publications

(25 citation statements)

References 57 publications

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“…This suggests that there was minimal downstream effect from extrasynaptic NMDAr. Instead, the increased activation of calpains in the frontal cortex and hippocampus of aged mice might be due to increased oxidative stress (Paramo et al 2013).…”

Section: Discussionmentioning

confidence: 97%

Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Zamzow¹,

Elias

Acosta

et al. 2016

AGE

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The N-methyl-D-aspartate receptor (NMDAr) is particularly vulnerable to aging. The GluN2B subunit of the NMDAr, compared to other NMDAr subunits, suffers the greatest losses of expression in the aging brain, especially in the frontal cortex. While expression levels of GluN2B mRNA and protein in the aged brain are well documented, there has been little investigation into agerelated posttranslational modifications of the subunit. In this study, we explored some of the mechanisms that may promote differences in the NMDAr complex in the frontal cortex of aged animals. Two ages of mice, 3 and 24 months, were behaviorally tested in the Morris water maze. The frontal cortex and hippocampus from each mouse were subjected to differential centrifugation followed by solubilization in Triton X-100. Proteins from Triton-insoluble membranes, Tritonsoluble membranes, and intracellular membranes/ cytosol were examined by Western blot. Higher levels of GluN2B tyrosine 1472 phosphorylation in frontal cortex synaptic fractions of old mice were associated with better reference learning but poorer cognitive flexibility. Levels of GluN2B phosphotyrosine 1336 remained steady, but there were greater levels of the calpain-induced 115 kDa GluN2B cleavage product on extrasynaptic membranes in these old good learners. There was an age-related increase in calpain activity, but it was not associated with better learning. These data highlight a unique aging change for aged mice with good spatial learning that might be detrimental to cognitive flexibility. This study also suggests that higher levels of truncated GluN2B on extrasynaptic membranes are not deleterious to spatial memory in aged mice.

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Section: Discussionmentioning

confidence: 97%

Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Zamzow¹,

Elias

Acosta

et al. 2016

AGE

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“…Thus enhancement of the cellular processes that suppress ROS generation or remove excess ROS may be effective in treating oxidative stress-induced diseases. Recently Nox proteins have been demonstrated to be major producers of ROS in CNS cells such as neurons, astrocytes, and microglia under pathophysiological conditions [16, 17]. Thus, inhibition of Nox proteins may present an effective mechanism to limit oxidative stress in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

Jia

et al. 2014

Oxidative Medicine and Cellular Longevity

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Background. Endogenous cannabinoid anandamide (AEA) protects neurons from oxidative injury in rodent models; however the mechanism of AEA-induced neuroprotection remains to be determined. Activation of neuronal NADPH oxidase 2 (Nox2) contributes to oxidative damage of the brain, and inhibition of Nox2 can attenuate cerebral oxidative stress. We aimed to determine whether the neuronal Nox2 was involved in protection mediated by AEA. Methods. The mouse hippocampal neuron cell line HT22 was exposed to hydrogen peroxide (H2O2) to mimic oxidative injury of neurons. The protective effect of AEA was assessed by measuring cell metabolic activity, apoptosis, lactate dehydrogenase (LDH) release, cellular morphology, intracellular reactive oxygen species (ROS), and antioxidant and oxidant levels and Nox2 expression. Results. HT22 cells exposed to H2O2 demonstrated morphological changes, decreased LDH release, reduced metabolic activity, increased levels of intracellular ROS and oxidized glutathione (GSSG), reduced levels of superoxide dismutase (SOD), and reduced glutathione (GSH) and increased expression of Nox2. AEA prevented these effects, a property abolished by simultaneous administration of CB1 antagonist AM251 or CB1-siRNA. Conclusion. Nox2 inhibition is involved in AEA-induced cytoprotection against oxidative stress through CB1 activation in HT22 cells.

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“…However, the calcium threshold to activate calpain is dramatically decreased during oxidative stress [51,52]. Ischemia-reperfusion damages the mitochondrial respiratory chain and markedly increases the ROS generation [53][54][55][56].…”

Section: Regulation Of Mitochondrial Calpain Activitymentioning

confidence: 99%

Heart mitochondria and calpain 1: Location, function, and targets

Chen¹,

Lesnefsky²

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Calpain 1 is an ubiquitous Ca(2+)-dependent cysteine protease. Although calpain 1 has been found in cardiac mitochondria, the exact location within mitochondrial compartments and its function remain unclear. The aim of the current review is to discuss the localization of calpain 1 in different mitochondrial compartments in relationship to its function, especially in pathophysiological conditions. Briefly, mitochondrial calpain 1 (mit-CPN1) is located within the intermembrane space and mitochondrial matrix. Activation of the mit-CPN1 within intermembrane space cleaves apoptosis inducing factor (AIF), whereas the activated mit-CPN1 within matrix cleaves complex I subunits and metabolic enzymes. Inhibition of the mit-CPN1 could be a potential strategy to decrease cardiac injury during ischemia-reperfusion.

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Calpain activation induced by glucose deprivation is mediated by oxidative stress and contributes to neuronal damage

Cited by 28 publications

References 57 publications

Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility

Anandamide Protects HT22 Cells Exposed to Hydrogen Peroxide by Inhibiting CB1 Receptor-Mediated Type 2 NADPH Oxidase

Heart mitochondria and calpain 1: Location, function, and targets

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