Metabotropic glutamate receptor/phospholipase C pathway
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Metabotropic glutamate receptor/phospholipase C pathway : a vulnerable target to Creutzfeldt-Jakob disease in the cerebral cortex. / Rodríguez, A; Freixes, M; Dalfó, E; Martín, M; Puig, B; Ferrer, I; Puig Martorell, Berta.
In: NEUROSCIENCE, Vol. 131, No. 4, 01.01.2005, p. 825-32.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Metabotropic glutamate receptor/phospholipase C pathway
T2 - a vulnerable target to Creutzfeldt-Jakob disease in the cerebral cortex
AU - Rodríguez, A
AU - Freixes, M
AU - Dalfó, E
AU - Martín, M
AU - Puig, B
AU - Ferrer, I
AU - Puig Martorell, Berta
PY - 2005/1/1
Y1 - 2005/1/1
N2 - Glutamate is the main excitatory neurotransmitter in the cerebral cortex. Altered glutamatergic transmission has been suggested as having a central role in many neurodegenerative diseases. Metabotropic glutamate receptors (mGluRs) are coupled to intracellular signal transduction via G proteins, and they mediate slower responses than ionotropic glutamate receptors. Group I mGluRs are positively coupled to phospholipase C beta1 (PLCbeta1). Creutzfeldt-Jakob disease (CJD) is a human transmissible spongiform encephalopathy associated with a dysfunction in the membrane glycoprotein PrP which is converted into an abnormal isoform, with a predominant beta-sheet structure, that is pathogenic and partially resistant to protease digestion. Proteins associated with the signal transduction of group I mGluRs were examined in the frontal cortex (area 8) of 12 cases with sCJD and four age-matched controls, by means of gel electrophoresis and Western blotting of total homogenates. Densitometric analysis of the bands demonstrated decreased expression levels of PLCbeta1 and PLCgamma, a non-related phospholipase which is a substrate of tyrosine kinase, in CJD cases when compared with controls. Novel protein kinase C delta (nPKCdelta) has also been found to be significantly decreased in CJD cases. However, no modifications in mGluR1 cPKCalpha expression levels are found in CJD when compared with controls. No modifications in PLCbeta1 solubility in PBS-, deoxycholate- and sodium dodecylsulphate-soluble fractions have been observed in CJD when compared with controls. Finally, no interactions between PLCbeta1 and PrP, as revealed by immunoprecipitation assays, have been found in CJD and controls. The present results show, for the first time, reduced expression levels of phospholipases, particularly PLCbeta1, which may interfere with group I mGluR signaling in the cerebral cortex in CJD. These abnormalities are not the result of abnormal PLC solubility or interactions with PrP. Selective involvement of group I mGluRs may have functional effects on glutamatergic transmission modulation and processing in CJD.
AB - Glutamate is the main excitatory neurotransmitter in the cerebral cortex. Altered glutamatergic transmission has been suggested as having a central role in many neurodegenerative diseases. Metabotropic glutamate receptors (mGluRs) are coupled to intracellular signal transduction via G proteins, and they mediate slower responses than ionotropic glutamate receptors. Group I mGluRs are positively coupled to phospholipase C beta1 (PLCbeta1). Creutzfeldt-Jakob disease (CJD) is a human transmissible spongiform encephalopathy associated with a dysfunction in the membrane glycoprotein PrP which is converted into an abnormal isoform, with a predominant beta-sheet structure, that is pathogenic and partially resistant to protease digestion. Proteins associated with the signal transduction of group I mGluRs were examined in the frontal cortex (area 8) of 12 cases with sCJD and four age-matched controls, by means of gel electrophoresis and Western blotting of total homogenates. Densitometric analysis of the bands demonstrated decreased expression levels of PLCbeta1 and PLCgamma, a non-related phospholipase which is a substrate of tyrosine kinase, in CJD cases when compared with controls. Novel protein kinase C delta (nPKCdelta) has also been found to be significantly decreased in CJD cases. However, no modifications in mGluR1 cPKCalpha expression levels are found in CJD when compared with controls. No modifications in PLCbeta1 solubility in PBS-, deoxycholate- and sodium dodecylsulphate-soluble fractions have been observed in CJD when compared with controls. Finally, no interactions between PLCbeta1 and PrP, as revealed by immunoprecipitation assays, have been found in CJD and controls. The present results show, for the first time, reduced expression levels of phospholipases, particularly PLCbeta1, which may interfere with group I mGluR signaling in the cerebral cortex in CJD. These abnormalities are not the result of abnormal PLC solubility or interactions with PrP. Selective involvement of group I mGluRs may have functional effects on glutamatergic transmission modulation and processing in CJD.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Blotting, Western
KW - Brain
KW - Brain Chemistry
KW - Cerebral Cortex
KW - Creutzfeldt-Jakob Syndrome
KW - Electrophoresis, Polyacrylamide Gel
KW - Female
KW - Humans
KW - Immunoprecipitation
KW - Isoenzymes
KW - Male
KW - Middle Aged
KW - Nerve Tissue Proteins
KW - Phospholipase C beta
KW - Prions
KW - Protein Kinase C
KW - Protein Kinase C-alpha
KW - Protein Kinase C-delta
KW - Receptors, Metabotropic Glutamate
KW - Type C Phospholipases
U2 - 10.1016/j.neuroscience.2004.12.023
DO - 10.1016/j.neuroscience.2004.12.023
M3 - SCORING: Journal article
C2 - 15749337
VL - 131
SP - 825
EP - 832
JO - NEUROSCIENCE
JF - NEUROSCIENCE
SN - 0306-4522
IS - 4
ER -