Protein kinase C activity, translocation, and conventional isoforms in aging rat brain

Battaini, F.; Elkabes, Stella; Bergamaschi, S.; Ladisa, Vito; Lucchi, Laura; Graan, P.N.E. de; Schuurman, T.; Wetsel, William C.; Trabucchi, Marco; Govoni, Stefano

doi:10.1016/0197-4580(94)00154-5

Cited by 75 publications

(54 citation statements)

References 61 publications

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“…1B) and hippocampus. 38 This effect is independent of the strain utilized because it is observed also in aged Fisher 344 rats. 39 …”

Section: Cpkcs Translocation Is Impaired In Aged Ratsmentioning

confidence: 73%

“…We found that Sprague-Dawley rat cortex shows age-related decrease in spite of an increase of PKC activity detected in the hippocampus and no change in cerebellum. 36 This effect proved to be strain-dependent because it was also observed in Fisher 344, 37 but not in Wistar rats, where kinase activity was unchanged in all brain areas (cortex, cerebellum, and hippocampus) and fractions (soluble and membrane) investigated 38 (FIG. 1A, for the activity in cortex).…”

Section: Kinase Activity Shows Strain and Substrate-dependent Changesmentioning

confidence: 99%

“…B-50 phosphorylation was instead increased in the hippocampal membranes from the same aged Wistar rats. 38 …”

Section: Kinase Activity Shows Strain and Substrate-dependent Changesmentioning

confidence: 99%

“…No modifications in the amount pattern of the different mRNAs were observed in aged Wistar rats, only a decrease in the α and β signal that is already present at 8 months of age in cortex. 38 Northern blot analysis allows quantification of mRNA in tissue homogenate but localized changes in specific brain regions may remain undetected due to the limitation of this approach. To further investigate any potential changes in PKC mRNA levels in discrete hippocampal and cortical regions, we performed in situ hybridization: aging did not modify in a significant manner the relative mRNA of the three calcium-dependent PKC isoforms in any area and subfield analyzed.…”

Section: Transcription and Translation Of Cpkcs In Agingmentioning

confidence: 99%

“…Calcium dependent PKC activity (A) and translocation (B) was assayed utilizing histone as substrate as described. 38 Calcium-independent PKC activity (C) and translocation (D) was assayed utilizing (Ser 25 ) PKC [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] as substrate as described. 41 Translocation is reported as ratio of activity in membranes and soluble fractions after treatment with PMA 160 nM for 15 min.…”

Section: Kinase Activity Shows Strain and Substrate-dependent Changesmentioning

confidence: 99%

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Protein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging

Battaini

2005

Annals of the New York Academy of Sciences

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Calcium/phospholipid-regulated protein kinase C (PKC) signalling is known to be involved in cellular functions relevant to brain health and disease, including ion channel modulation, receptor regulation, neurotransmitter release, synaptic plasticity, and survival. Brain aging is characterized by altered neuronal molecular cascades and interneuronal communication in response to various stimuli. In the last few years we have provided evidence that in rodents, despite no changes in PKC isoform levels (both calcium dependent and calcium independent), the activation/translocation process of the calcium-dependent and -independent kinases and the content of the adaptor protein RACK1 (receptor for activated C kinase-1) are deficient in physiological brain aging. Moreover, human studies have shown that PKC and its adaptor protein RACK1 are also interdependent in pathological brain aging (e.g., Alzheimer's disease); in fact, calcium-dependent PKC translocation and RACK1 levels are both deficient in an area-selective manner. These data point to the notion that, in addition to a well-described lipid environment alteration, changes in protein-protein interactions may impair the mechanisms of PKC activation in aging. It is interesting to note that interventions to counteract the age-related functional loss also restore PKC activation and the adaptor protein machinery expression. A better insight into the factors controlling PKC activation may be important not only to elucidate the molecular basis of signal transmission, but also to identify new strategies to correct or even to prevent agedependent alterations in cell-to-cell communication.

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“…1B) and hippocampus. 38 This effect is independent of the strain utilized because it is observed also in aged Fisher 344 rats. 39 …”

Section: Cpkcs Translocation Is Impaired In Aged Ratsmentioning

confidence: 73%

Section: Kinase Activity Shows Strain and Substrate-dependent Changesmentioning

confidence: 99%

“…B-50 phosphorylation was instead increased in the hippocampal membranes from the same aged Wistar rats. 38 …”

Section: Kinase Activity Shows Strain and Substrate-dependent Changesmentioning

confidence: 99%

Section: Transcription and Translation Of Cpkcs In Agingmentioning

confidence: 99%

Section: Kinase Activity Shows Strain and Substrate-dependent Changesmentioning

confidence: 99%

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Protein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging

Battaini

2005

Annals of the New York Academy of Sciences

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Individual differences in spatial memory among aged rats are related to hippocampal PKCγ immunoreactivity

Colombo

Gallagher

2002

Hippocampus

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We reported previously that the extent of spatial memory impairment among aged rats was correlated positively with levels of protein kinase Cgamma in hippocampal homogenates measured by quantitative Western blotting (Colombo et al., 1997). In the current study, immunocytochemistry was used to test whether the relationship between elevated PKC-gamma and memory impairment among aged rats could be localized further within regions of the hippocampus. Six- and 24-month-old male Long-Evans rats were first trained in the water maze on a standard place-learning task and then trained 2 weeks later on a transfer task designed for rapid acquisition. In comparison with young rats, aged rats with impaired spatial memory had increased PKCgamma-immunoreactivity (PKCgamma-ir) in CA1 of the hippocampus, but not the dentate gyrus. In addition, PKCgamma-ir in CA1 was correlated positively with spatial memory impairment among aged rats on the standard place-learning and the transfer training tasks. The current results are consistent with our previous report of PKCgamma in hippocampal homogenates, and show further that the relationships between PKCgamma-ir and memory impairments among aged rats are most evident in area CA1. Thus age-related impairments of spatial memory, as well as deficits in the flexible use of previously acquired information, may result from dysregulation of PKCgamma.

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Aging‐related alterations in the distribution of Ca²⁺‐dependent PKC isoforms in rabbit hippocampus

Zee

Palm²,

O’Connor

et al. 2004

Hippocampus

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The immunocytochemical and subcellular localization of the Ca2+‐dependent protein kinase C (cPKC) isoforms (PKCα, β1, β2, and γ) was examined in rabbit hippocampus of young (3 months of age; n = 11) and aging (36 months of age; n = 14) subjects. Detailed immunocytochemical analyses revealed a significant increase in PKCβ1, β2, and γ immunoreactivity in principal cell bodies and associated dendrites, and interneurons of the hilar region in the aging rabbits. The number of PKCα‐ and γ‐positive interneurons in the aging stratum oriens declined significantly. PKCα was least affected in principal cells, showing an increase in immunostaining in granule cells only. Weakly PKC‐positive principal cells intermingled between densely stained ones were seen in parts of the hippocampus in most of the aging rabbits, showing that the degree of aging‐related alterations in PKC‐immunoreactivity varies between neurons. Changes in PKC expression in the molecular and subgranular layer of the aging dentate gyrus suggested a reorganization of PKC‐positive afferents to this region. Western blot analysis revealed a significant loss of PKC in the pellet fraction for all isoforms, and a tendency for increased levels of cytosolic PKC. However, no significant changes were found in total PKC content for any PKC isoform. A concurrent dramatic loss of the PKC anchoring protein receptor for activated C kinase (RACK1) in the pellet fraction was shown by Western blotting. These findings suggest that the loss of RACK1 contributes to the dysregulation of the PKC system in the aging rabbit hippocampus. The enhanced PKC‐immunoreactivity might relate to reduced protein‐protein interactions of PKC with the anchoring protein RACK1 leading to increased access of the antibodies to the antigenic site. In conclusion, the results suggest that memory deficits in aging rabbits are (in part) caused by dysregulation of subcellular PKC localization in hippocampal neurons. © 2004 Wiley‐Liss, Inc.

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Protein kinase C activity, translocation, and conventional isoforms in aging rat brain

Cited by 75 publications

References 61 publications

Protein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging

Protein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging

Individual differences in spatial memory among aged rats are related to hippocampal PKCγ immunoreactivity

Aging‐related alterations in the distribution of Ca²⁺‐dependent PKC isoforms in rabbit hippocampus

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Protein kinase C activity, translocation, and conventional isoforms in aging rat brain

Cited by 75 publications

References 61 publications

Protein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging

Protein Kinase C Signal Transduction Regulation in Physiological and Pathological Aging

Individual differences in spatial memory among aged rats are related to hippocampal PKCγ immunoreactivity

Aging‐related alterations in the distribution of Ca2+‐dependent PKC isoforms in rabbit hippocampus

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Aging‐related alterations in the distribution of Ca²⁺‐dependent PKC isoforms in rabbit hippocampus