Oral aluminum alters in vitro protein phosphorylation and kinase activities in rat brain

Johnson, Gail V.W.; Cogdill, Keith W.; Jope, Richard S.

doi:10.1016/0197-4580(90)90547-d

Cited by 49 publications

(22 citation statements)

References 32 publications

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“…The largest inhibition was observed in the cerebral cortex (47.73%) followed by the hippocampus (45.95%) and the corpus striatum (38.74%) [20]. However, contrasting findings were determined by Johnson and coworkers who showed that aluminum sulfate, when given orally for a period of 4 months to male SpragueDawley rats, showed an increase in PKC specific activity by 60% and total activity by 70% in the soluble fraction of cerebral cortex homogenates [69]. The different effects of aluminum could be attributed to the mode of intake reflecting differences in concentration of aluminum absorbed and its distribution to the brain or the duration of exposure.…”

Section: Gpcrmentioning

confidence: 78%

“…Normally PKC is translocated from the cytosol to the membrane when it is activated. Application of Al 3+ caused a 70% increase in the total activity of PKC resulting in a greater fraction of it being translocated to the membrane, and hence the presence of greater fraction of PKC in particulate fraction compared to the soluble fraction [69].…”

Section: Protein Kinase C (Pkc)mentioning

confidence: 99%

“…Lead modulated Gs, adenylate cyclase, PKC, and CaM [10,53,54,85]. Adenylate cyclase activity was also modulated by cadmium, mercury, and zinc [54,82,83] while PKC was inhibited by lead, aluminum, and nickel, [20,69,85,86], and IP 3 was inhibited by cisplatin and arsenic [88]. Intracellular calcium was affected through interference with several targets including voltagegated calcium channels, Ca 2+ ATPases, and intracellular pathways.…”

Section: Neurofilaments and Microtubules In Vivo Exposure Ofmentioning

confidence: 99%

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Metal toxicity at the synapse: presynaptic, postsynaptic and long-term effects

Ghazala

Sadiq

Chowdhury

et al. 2010

Qatar Foundation Annual Research Forum Proceedings

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Metal neurotoxicity is a global health concern. This paper summarizes the evidence for metal interactions with synaptic transmission and synaptic plasticity. Presynaptically metal ions modulate neurotransmitter release through their interaction with synaptic vesicles, ion channels, and the metabolism of neurotransmitters (NT). Many metals (e.g., Pb 2+ , Cd 2+ , and Hg + ) also interact with intracellular signaling pathways. Postsynaptically, processes associated with the binding of NT to their receptors, activation of channels, and degradation of NT are altered by metals. Zn 2+ , Pb 2+ , Cu 2+ , Cd 2+ , Ni 2+ , Co 2+ , Li 3+ , Hg + , and methylmercury modulate NMDA, AMPA/kainate, and/or GABA receptors activity. Al 3+ , Pb 2+ , Cd 2+ , and As 2 O 3 also impair synaptic plasticity by targeting molecules such as CaM, PKC, and NOS as well as the transcription machinery involved in the maintenance of synaptic plasticity. The multiple effects of metals might occur simultaneously and are based on the specific metal species, metal concentrations, and the types of neurons involved.

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Section: Gpcrmentioning

confidence: 78%

Section: Protein Kinase C (Pkc)mentioning

confidence: 99%

Section: Neurofilaments and Microtubules In Vivo Exposure Ofmentioning

confidence: 99%

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Metal toxicity at the synapse: presynaptic, postsynaptic and long-term effects

Ghazala

Sadiq

Chowdhury

et al. 2010

Qatar Foundation Annual Research Forum Proceedings

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“…In rabbit brain (21,23) and in cultured neurons (16), A13÷-induced aggregates contain phosphorylated "r. Oral administration of A13÷ causes an increase in the activities of some protein kinases in rat brain (17). It was suggested that A13+ affects protein phosphorylation and pro- tein kinase activities in vivo (17). To test whether AP + alters phosphorylation of r by directly affecting "r specific kinase or r, we investigated the effect of A12(SO4) 3 on the activity ofNCLK.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, exposure to A13+ causes an increase in the phosphorylation of r in neuroblastoma cells (16). Oral administration of A13÷ alters protein phosphorylation and activates some protein kinases in rat brain (17) and these kinases phosphorylate r in vitro (18). In vitro, A13+ induces phosphorylation of "r (19) and inhibits dephosphorylation of'r in rat brain synaptosomal fractions (20).…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation sensitizes microtubule-associated protein τ to Al3+-induced aggregation

Kenneth

Sun

et al. 1998

Neurochem Res

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In Alzheimer's disease the microtubule-associated protein tau becomes hyperphosphorylated and aggregates into paired helical filaments (PHFs). Although the biochemical basis of the aggregation of tau into PHFs is not very clear, Al3+ has been suggested to play some role. Previous studies have shown that Al3+ alters the phosphorylation state and causes aggregation of tau in experimental animals and cultured neurons. In this study Al3+ inhibited phosphorylation of tau by neuronal cdc2-like kinase and dephosphorylation of phosphorylated tau by phosphatase 2B. These inhibitions are very likely due to Al(3+)-induced aggregations of various proteins present in phosphorylation/dephosphorylation assay mixtures since Al3+ caused aggregations of all proteins examined. Furthermore, compared to other proteins, tau displayed only an average sensitivity towards Al(3+)-induced aggregation. However upon phosphorylation, tau's sensitivity towards Al3+ increased 3.5 fold. In the presence of the metal chelator EDTA, Al(3+)-induced aggregates of tau became soluble, whereas Al(3+)-induced phosphorylated tau aggregates were insoluble in the buffer containing EDTA and remained insensitive to proteolysis. Our data suggest that phosphorylation sensitizes tau to Al3+ and phosphorylated tau transforms irreversibly into a phosphatase and protease resistant aggregate in presence of this metal ion.

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