La maladie de Parkinson au Canada (serveur d'exploration)

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Peptidase activities of the 20/26S proteasome and a novel protease in human brain

Identifieur interne : 000246 ( PascalFrancis/Curation ); précédent : 000245; suivant : 000247

Peptidase activities of the 20/26S proteasome and a novel protease in human brain

Auteurs : Sophie Vigouroux [France] ; Yoshiaki Furukawa [Canada] ; Luc Farout [France] ; Stephen J. Kish [Canada] ; Marièle Briand [France] ; Yves Briand [France]

Source :

RBID : Pascal:03-0245854

Descripteurs français

English descriptors

Abstract

Many neurodegenerative diseases are characterized by ubiquitin-positive protein aggregates or inclusion bodies. Ubiquitin-conjugated proteins are degraded by the 20/26S proteasome, and reduced proteasome peptidase activities in brain homogenates have been reported in pathologic lesions of Parkinson's and Alzheimer's diseases. However, it is unknown whether crude extracts of human brain contain other proteases having peptidase activities. We found a novel protease of molecular weight of approximately 105 kDa in normal human brain, which exhibited trypsin-like (T-L) and chymotrypsin-like (ChT-L) activities (corresponding to 52% and 21% of the total activities in crude extracts) but not peptidyl glutamyl peptide hydrolase activity. Both T-L and ChT-L activities of this protease were partially inhibited by proteasome inhibitors (MG132, lactacystin) and, in contrast to those of the proteasome, also by sodium dodecyl sulfate. A simple method to obtain a brain fraction specific to the 20/26S proteasome was developed. Our human brain data suggest that T-L and ChT-L activity levels of the proteasome reported previously may include those of the 105 kDa protease, an enzyme of as yet unknown biological significance, and that it is necessary to separate the proteasome from this protease to evaluate the actual status of the ubiquitin-proteasome system in neurodegenerative disorders.
pA  
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A02 01      @0 JONRA9
A03   1    @0 J. neurochem.
A05       @2 84
A06       @2 2
A08 01  1  ENG  @1 Peptidase activities of the 20/26S proteasome and a novel protease in human brain
A11 01  1    @1 VIGOUROUX (Sophie)
A11 02  1    @1 FURUKAWA (Yoshiaki)
A11 03  1    @1 FAROUT (Luc)
A11 04  1    @1 KISH (Stephen J.)
A11 05  1    @1 BRIAND (Marièle)
A11 06  1    @1 BRIAND (Yves)
A14 01      @1 Laboratoire de Biochimie Appliquée - UA INRA 995, Université Blaise Pascal @2 Aubière @3 FRA @Z 1 aut. @Z 3 aut. @Z 5 aut. @Z 6 aut.
A14 02      @1 Movement Disorders Research Laboratory, Centre for Addiction and Mental Health-Clarke Division @2 Toronto, Ontario @3 CAN @Z 2 aut.
A14 03      @1 Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health-Clarke Division @2 Toronto, Ontario @3 CAN @Z 4 aut.
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A21       @1 2003
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C01 01    ENG  @0 Many neurodegenerative diseases are characterized by ubiquitin-positive protein aggregates or inclusion bodies. Ubiquitin-conjugated proteins are degraded by the 20/26S proteasome, and reduced proteasome peptidase activities in brain homogenates have been reported in pathologic lesions of Parkinson's and Alzheimer's diseases. However, it is unknown whether crude extracts of human brain contain other proteases having peptidase activities. We found a novel protease of molecular weight of approximately 105 kDa in normal human brain, which exhibited trypsin-like (T-L) and chymotrypsin-like (ChT-L) activities (corresponding to 52% and 21% of the total activities in crude extracts) but not peptidyl glutamyl peptide hydrolase activity. Both T-L and ChT-L activities of this protease were partially inhibited by proteasome inhibitors (MG132, lactacystin) and, in contrast to those of the proteasome, also by sodium dodecyl sulfate. A simple method to obtain a brain fraction specific to the 20/26S proteasome was developed. Our human brain data suggest that T-L and ChT-L activity levels of the proteasome reported previously may include those of the 105 kDa protease, an enzyme of as yet unknown biological significance, and that it is necessary to separate the proteasome from this protease to evaluate the actual status of the ubiquitin-proteasome system in neurodegenerative disorders.
C02 01  X    @0 002B17G
C03 01  X  FRE  @0 Peptidases @2 FE @5 01
C03 01  X  ENG  @0 Peptidases @2 FE @5 01
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C03 02  X  FRE  @0 Multicatalytic endopeptidase complex @2 FE @5 02
C03 02  X  ENG  @0 Multicatalytic endopeptidase complex @2 FE @5 02
C03 02  X  SPA  @0 Multicatalytic endopeptidase complex @2 FE @5 02
C03 03  X  FRE  @0 Omptin @2 FE @5 03
C03 03  X  ENG  @0 Omptin @2 FE @5 03
C03 03  X  SPA  @0 Omptin @2 FE @5 03
C03 04  X  FRE  @0 Ubiquitine @5 04
C03 04  X  ENG  @0 Ubiquitin @5 04
C03 04  X  SPA  @0 Ubiquitina @5 04
C03 05  X  FRE  @0 Expression génique @5 05
C03 05  X  ENG  @0 Gene expression @5 05
C03 05  X  SPA  @0 Expresión genética @5 05
C03 06  X  FRE  @0 Activité enzymatique @5 07
C03 06  X  ENG  @0 Enzymatic activity @5 07
C03 06  X  SPA  @0 Actividad enzimática @5 07
C03 07  X  FRE  @0 Démence Alzheimer @5 09
C03 07  X  ENG  @0 Alzheimer disease @5 09
C03 07  X  SPA  @0 Demencia Alzheimer @5 09
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C03 09  X  FRE  @0 Homme @5 54
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C03 09  X  SPA  @0 Hombre @5 54
C07 01  X  FRE  @0 Hydrolases @2 FE
C07 01  X  ENG  @0 Hydrolases @2 FE
C07 01  X  SPA  @0 Hydrolases @2 FE
C07 02  X  FRE  @0 Enzyme
C07 02  X  ENG  @0 Enzyme
C07 02  X  SPA  @0 Enzima
C07 03  X  FRE  @0 Serine endopeptidases @2 FE
C07 03  X  ENG  @0 Serine endopeptidases @2 FE
C07 03  X  SPA  @0 Serine endopeptidases @2 FE
C07 04  X  FRE  @0 Encéphale pathologie @5 20
C07 04  X  ENG  @0 Cerebral disorder @5 20
C07 04  X  SPA  @0 Encéfalo patología @5 20
C07 05  X  FRE  @0 Système nerveux central @5 21
C07 05  X  ENG  @0 Central nervous system @5 21
C07 05  X  SPA  @0 Sistema nervioso central @5 21
C07 06  X  FRE  @0 Système nerveux pathologie @5 22
C07 06  X  ENG  @0 Nervous system diseases @5 22
C07 06  X  SPA  @0 Sistema nervioso patología @5 22
C07 07  X  FRE  @0 Système nerveux central pathologie @5 23
C07 07  X  ENG  @0 Central nervous system disease @5 23
C07 07  X  SPA  @0 Sistema nervosio central patología @5 23
C07 08  X  FRE  @0 Maladie dégénérative @5 24
C07 08  X  ENG  @0 Degenerative disease @5 24
C07 08  X  SPA  @0 Enfermedad degenerativa @5 24
C07 09  X  FRE  @0 Extrapyramidal syndrome @5 25
C07 09  X  ENG  @0 Extrapyramidal syndrome @5 25
C07 09  X  SPA  @0 Extrapiramidal síndrome @5 25
N21       @1 153

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<div type="abstract" xml:lang="en">Many neurodegenerative diseases are characterized by ubiquitin-positive protein aggregates or inclusion bodies. Ubiquitin-conjugated proteins are degraded by the 20/26S proteasome, and reduced proteasome peptidase activities in brain homogenates have been reported in pathologic lesions of Parkinson's and Alzheimer's diseases. However, it is unknown whether crude extracts of human brain contain other proteases having peptidase activities. We found a novel protease of molecular weight of approximately 105 kDa in normal human brain, which exhibited trypsin-like (T-L) and chymotrypsin-like (ChT-L) activities (corresponding to 52% and 21% of the total activities in crude extracts) but not peptidyl glutamyl peptide hydrolase activity. Both T-L and ChT-L activities of this protease were partially inhibited by proteasome inhibitors (MG132, lactacystin) and, in contrast to those of the proteasome, also by sodium dodecyl sulfate. A simple method to obtain a brain fraction specific to the 20/26S proteasome was developed. Our human brain data suggest that T-L and ChT-L activity levels of the proteasome reported previously may include those of the 105 kDa protease, an enzyme of as yet unknown biological significance, and that it is necessary to separate the proteasome from this protease to evaluate the actual status of the ubiquitin-proteasome system in neurodegenerative disorders.</div>
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<fC03 i1="03" i2="X" l="FRE">
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<s2>FE</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Omptin</s0>
<s2>FE</s2>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Omptin</s0>
<s2>FE</s2>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Ubiquitine</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Ubiquitin</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Ubiquitina</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Expression génique</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Gene expression</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Expresión genética</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Activité enzymatique</s0>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Enzymatic activity</s0>
<s5>07</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Actividad enzimática</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Démence Alzheimer</s0>
<s5>09</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Alzheimer disease</s0>
<s5>09</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Demencia Alzheimer</s0>
<s5>09</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Parkinson maladie</s0>
<s5>12</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>Parkinson disease</s0>
<s5>12</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Parkinson enfermedad</s0>
<s5>12</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE">
<s0>Homme</s0>
<s5>54</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG">
<s0>Human</s0>
<s5>54</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA">
<s0>Hombre</s0>
<s5>54</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Hydrolases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Enzyme</s0>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Enzyme</s0>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Enzima</s0>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Serine endopeptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Serine endopeptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Serine endopeptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Encéphale pathologie</s0>
<s5>20</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Cerebral disorder</s0>
<s5>20</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Encéfalo patología</s0>
<s5>20</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Système nerveux central</s0>
<s5>21</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Central nervous system</s0>
<s5>21</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Sistema nervioso central</s0>
<s5>21</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Système nerveux pathologie</s0>
<s5>22</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Nervous system diseases</s0>
<s5>22</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Sistema nervioso patología</s0>
<s5>22</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Système nerveux central pathologie</s0>
<s5>23</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Central nervous system disease</s0>
<s5>23</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Sistema nervosio central patología</s0>
<s5>23</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE">
<s0>Maladie dégénérative</s0>
<s5>24</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG">
<s0>Degenerative disease</s0>
<s5>24</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA">
<s0>Enfermedad degenerativa</s0>
<s5>24</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE">
<s0>Extrapyramidal syndrome</s0>
<s5>25</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG">
<s0>Extrapyramidal syndrome</s0>
<s5>25</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA">
<s0>Extrapiramidal síndrome</s0>
<s5>25</s5>
</fC07>
<fN21>
<s1>153</s1>
</fN21>
</pA>
</standard>
</inist>
</record>

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