Evidence for the presence of high‐Mr microtubule‐associated proteins and their Ca2+‐dependent proteolysis in synaptosomal cytosol

Burgoyne, Robert D.; Cumming, R. L. C.

doi:10.1016/0014-5793(82)80933-2

Cited by 30 publications

(7 citation statements)

References 22 publications

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“…Specific roles and substrates for the proteinase in particular tissues have been argued by many workers, such as oestrogen receptors in uterus (Puca et al, 1977), progesterone receptors in oviduct (Vedeckis et al, 1980), platelet proteins (Fox et al, 1983) and neurofilament proteins (Baudry & Lynch, 1980;Burgoyne & Cumming, 1982;Ishizaki et al, 1983), in addition to the original suggestion of a role in muscle Z-line degradation (Reddy et al, 1975;Dayton et al, 1976). In none of these cases has it yet been unequivocally shown that the proteinase and the proposed substrate have access to each other and to sufficient Ca2 + in the native tissue.…”

Section: Pregnant and Involuting Uterusmentioning

confidence: 99%

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues

Elce¹,

Baenziger²,

Young³

1984

Biochemical Journal

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Rat uteri were taken at various stages of pregnancy and involution post partum, and several other tissues were taken from pregnant and non-pregnant animals. Portions of each tissue were homogenized in the presence of proteinase inhibitors, and the amounts of the high-Ca2+-requiring Ca2+-activated proteinase in the supernatants were measured by a two-site immunoradiometric assay using 125I-immunoglobulin G. The proteinase was shown, by protein blotting, to be immunologically identical in all tissues. The amounts in the various tissues, expressed in units of proteinase activity/g wet wt., were: lung, 95; kidney and small intestine, 42; liver, 20; brain, heart and skeletal muscle, 13. Uterine wet weight increased at the end of pregnancy by about 8-fold, but the amounts of proteinase per uterus increased by about 22-fold; alternatively, expressed in units of proteinase activity/g wet wt., the mean uterine values were: non-pregnant, 28.6; term-pregnant, 77.0. As the wet weight of the uterus fell rapidly during involution, the amounts of proteinase activity remained relatively high. The data suggest that the Ca2+-activated proteinase may have some role in tissue resorption during uterine involution, but the high proteinase activity present before parturition must be regulated in ways which are not yet clear.

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Section: Pregnant and Involuting Uterusmentioning

confidence: 99%

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues

Elce¹,

Baenziger²,

Young³

1984

Biochemical Journal

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“…Among these, the neutral cysteine protease calpain (EC 3.4.22.17) attracted our attention as a means of clarifying the pathogenesis of postischaemic delayed neuronal death (Fukuda, 1990;Saido et al, 1993;Ostwald 1994). Upon activation in vitro, calpain is known to degrade/modulate major neuronal structural proteins (Sandoval and Weber, 1978;Schlaepfer, 1979;Burgoyne and Cumming, 1982;Baudry, 1986;Nixon, 1986;Siman and Noszek, 1988;Arai et al, 1991) such as tubulin, microtubuleassociated proteins, fodrin and neurofilaments.…”

Section: Introductionmentioning

confidence: 99%

Transient Brain Ischaemia Provokes Ca²⁺, PIP₂ and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

Yamashima

Saido

Takita

et al. 1996

Eur J of Neuroscience

145

130

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To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated mu-calpain demonstrated mu-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of mu-calpain, and increased immunostaining for inactivated and activated forms of mu- and m-calpains and for PIP2. Activated mu-calpain and PIP2 were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca2+ mobilization with increased PIP2 immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca2+ and PIP2 breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.

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“…In fact, it has been reported that intracerebro-ventricular injection of N-methyl-D-aspartate causes substantial proteolysis of MAP-2 when assayed 6-24 h after drug application [50]. In addition, MAP-2 is an excellent substrate for calpain I (Ca2'-dependent protease) [36], which is greatly activated by N-methyl-D-aspartate. However, our results do not support such hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…In the latter case, the tubulin binding region is phosphorylated, as occurs with microtubule-associated Tau protein [35]. It is strongly suggested that the phosphorylation state of MAP-2 is related to its ability to promote microtubule assembly [36,371. More recently, it has been indicated that activation of N-methyl-Daspartate receptors induces a rapid dephosphorylation of MAP-2 in hippocampal slices [38].…”

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confidence: 99%

Rapid dephosphorylation of microtubule‐associated protein 2 in the rat brain hippocampus after pentylenetetrazole‐induced seizures

Díez‐Guerra¹,

Ávila²

1993

European Journal of Biochemistry

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We have studied the effect of Pentylenetetrazole (PTZ)-induced seizures on the state of phosphorylation of microtubule-associated protein 2 (MAP-2) from rat hippocampus. A method for the in vivo 32P-labeling of hippocampal proteins has been established, consisting of intracerebro-ventricular injection of "PO, of high specific activity. The results obtained indicate that PTZ induces a rapid and transient dephosphorylation of high-molecular-mass MAP-2, which is prevented when the Nmethyl+-aspartate receptor antagonist MK-801 is previously administered. Phosphopeptide mapping of 32P-labeled MAP-2 obtained from hippocampi of PTZ-treated rats reveals a pattern of phosphorylation distinct from that obtained from control saline-treated rats or MK-801 plus PTZ treated rats. We discuss the possible implications of N-methyl-D-aspartate-receptor activation and MAP-2 dephosphorylation on the plastic changes induced in rat brain hippocampus after induced epileptiform activity.It has been long recognized that experimental paradigms such as kindling or chemically induced seizures profoundly alter the pattern of synaptic connectivity within the limbic system [l -41. The hippocampal formation constitutes a clear target for the plastic changes associated with sustained stimulation of limbic pathways and development of generalized convulsions. There have been reported alterations in the content and release of different neurotransmitters [5 -81, the expression of a variety of neuropeptides [9-131, neurotrophic factors [14-161 and the activity of several enzymes [17-211 after experimentally induced seizures. In the longer term, morphological alterations such as aberrant axon sprouting and de novo formation of synaptic contacts appear [22-261. The alterations in neuronal morphology have to be based on changes in the neuronal cytoskeleton, which is responsible for the initiation and stabilization of the new fibers and synaptic contacts. In this respect, modifications on microtubuleassociated protein 2 (MAP-2) may play a role in such changes 1271. These modifications could include phosphorylation-dephosphorylation since this mechanism has been implicated in neural transmission [28]. High-molecular-mass MAP-2 is a neuron-specific protein which promotes the assembly of microtubules in v i m , localizes in the dendritic compartment of the neuron and is also present in the dendritic spines [ suggested that the phosphorylation state of MAP-2 is related to its ability to promote microtubule assembly [36, 371. More recently, it has been indicated that activation of N-methyl-Daspartate receptors induces a rapid dephosphorylation of MAP-2 in hippocampal slices [38].Pentylenetetrazole (PTZ) is a drug with potent convulsant effects. Its effects seem to be mediated by inhibition of 4-aminobutyric-acid-A receptors, since PTZ has been shown to block 4-aminobutyric-acid-dependent chloride influx [39]. Intraperitoneally (ip) administered PTZ quickly evokes the appearance of strong seizures which are accompanied by a dramatic increase in the express...

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Evidence for the presence of high‐M_r microtubule‐associated proteins and their Ca²⁺‐dependent proteolysis in synaptosomal cytosol

Cited by 30 publications

References 22 publications

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues

Transient Brain Ischaemia Provokes Ca²⁺, PIP₂ and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

Rapid dephosphorylation of microtubule‐associated protein 2 in the rat brain hippocampus after pentylenetetrazole‐induced seizures

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Evidence for the presence of high‐Mr microtubule‐associated proteins and their Ca2+‐dependent proteolysis in synaptosomal cytosol

Cited by 30 publications

References 22 publications

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues

Ca2+-activated proteinase in the rat. Quantification by immunoassay in the uterus during pregnancy and involution, and in other tissues

Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

Rapid dephosphorylation of microtubule‐associated protein 2 in the rat brain hippocampus after pentylenetetrazole‐induced seizures

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Product

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Evidence for the presence of high‐M_r microtubule‐associated proteins and their Ca²⁺‐dependent proteolysis in synaptosomal cytosol

Transient Brain Ischaemia Provokes Ca²⁺, PIP₂ and Calpain Responses Prior to Delayed Neuronal Death in Monkeys