oru.sePublikasjoner
12345674 of 16
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Functional analysis of the proteasome in eukaryotic organisms
Örebro universitet, Institutionen för medicinska vetenskaper.
2020 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Proteasome degradation machinery is responsible for the turnover of a huge variety of normal and abnormal proteins, thus regulating a plethora of cellular processes. Aging is an inevitable biological process that is characterized by reduced proteasome function that leads to proteotoxic stress. Compound-related interventions, that ameliorate proteasome system collapse, retard aging process. In the present thesis, 18α-glycyrrhetinic acid (18α-GA), a natural compound with known proteasome activating properties in cells, was indicated to activate proteasome also in the multicellular organism Caenorhabditis elegans (C. elegans). Evaluation of the antiaging and protein anti-aggregation effects of this bioactive compound indicated that 18α-GA promoted longevity in nematodes through proteasome-and SKN-1-mediated activation and decelerated Alzheimer’sdisease progression and neuropathology both in nematodes and neuronal cells. Additionally, the crosstalk between protein synthesis and proteasome-mediated protein degradation was analyzed in eukaryotic organisms under various cellular conditions. Protein synthesis inhibition was observed to increase proteasome function and assembly in human primary embryonic fibroblasts, with heat shock protein chaperone machinery to contribute to the elevated proteasome assembly. Alternatively, protein synthesis inhibition increased the protein levels of specific proteasome subunits without influencing the proteasome activity in C. elegans. Furthermore, proteasome activation by means which have also pro-longevity effects decreased the protein synthesis rate both in human fibroblast cellsand nematodes. This thesis suggests: 1) that a diet-derived compound could act as a pro-longevity and anti-aggregation agent in the context of amulticellular organism and 2) the existence of a complex interplay between anabolic and catabolic processes under different cellular conditions, across species.

sted, utgiver, år, opplag, sider
Örebro: Örebro University , 2020. , s. 116
Serie
Örebro Studies in Medicine, ISSN 1652-4063 ; 208
Emneord [en]
Proteasome, Proteasome activation, Protein synthesis inhibition, Hsp70, Hsp90, Proteostasis, Aging, Alzheimer’s disease, Caenorhabditis elegans, Lifespan extension, SKN-1
HSV kategori
Identifikatorer
URN: urn:nbn:se:oru:diva-79875ISBN: 978-91-7529-330-1 (tryckt)OAI: oai:DiVA.org:oru-79875DiVA, id: diva2:1392955
Disputas
2020-04-23, Örebro universitet, Campus USÖ, hörsal C3, Södra Grev Rosengatan 32, Örebro, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2020-02-14 Laget: 2020-02-14 Sist oppdatert: 2020-04-07bibliografisk kontrollert
Delarbeid
1. 18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures
Åpne denne publikasjonen i ny fane eller vindu >>18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures
Vise andre…
2016 (engelsk)Inngår i: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 25, nr 16, s. 855-869Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression.

Results: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment.

Innovation: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism.

Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet.

sted, utgiver, år, opplag, sider
New Rochelle, USA: Mary Ann Liebert, 2016
Emneord
Proteasome activation, lifespan extension, aging, Alzheimer’s disease, aggregation, proteostasis
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-49639 (URN)10.1089/ars.2015.6494 (DOI)000388262600001 ()26886723 (PubMedID)
Merknad

Funding Agencies:

U.S. National Institutes of Health National Center for Research Resources

Thales GenAge QALHS AP:10479/3.7.12 MIS380228

MAESTRO by the European Union (European Social Fund)

Operational Program, Education and Lifelong Learning, of the National Strategic Reference Framework (NSRF)

European Union 266486

IKYDA fellowship

Empirikion Foundation Scientific Project

John S. Latsis Public Benefit Foundation

Academy of Finland 259797

COST Actions PROTEOS-TASIS BM1307

GENiE BM1408

COST (European Cooperation in Science and Technology)

Tilgjengelig fra: 2016-04-20 Laget: 2016-04-05 Sist oppdatert: 2020-03-30bibliografisk kontrollert
2. Protein synthesis inhibition induces proteasome assembly and function
Åpne denne publikasjonen i ny fane eller vindu >>Protein synthesis inhibition induces proteasome assembly and function
2019 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 514, nr 1, s. 224-230Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Protein synthesis and degradation balance have a crucial role in maintenance of cellular homeostasis and function. The ubiquitin-proteasome system is one of the major cellular proteolytic machineries responsible for the removal of normal, abnormal, denatured or in general damaged proteins. Proteasome is a multisubunit enzyme that consists of the 20S core and the 19S regulatory complexes giving rise to multiple active forms. In the present study we investigated the crosstalk between protein synthesis and proteasome-mediated protein degradation. Pharmacological protein synthesis inhibition led to increased proteasome function and assembly of 30S/26S proteasome complexes, in human primary embryonic fibroblasts. The enhancement in proteasome function counted for the degradation of ubiquitinated, misfolded and oxidized proteins. Additionally, it was found that heat shock proteins 70 and 90 are probably involved in the elevated proteasome assembly. Our results provide an insight on how the mechanisms of protein synthesis, protein degradation and heat shock protein chaperones machinery interact under various cellular conditions.

sted, utgiver, år, opplag, sider
Elsevier, 2019
Emneord
Proteasome, Proteasome activation, Protein synthesis inhibition, Hsp70, Hsp90
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-79901 (URN)10.1016/j.bbrc.2019.04.114 (DOI)000469406800033 ()31029420 (PubMedID)2-s2.0-85064700180 (Scopus ID)
Merknad

Funding Agencies:

Research Funding Program: Thales "GenAge" - European Union  QALHS AP:10479/3.7.12 MIS380228

Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF) 

Tilgjengelig fra: 2020-02-14 Laget: 2020-02-14 Sist oppdatert: 2020-03-30bibliografisk kontrollert
3. Study of the effects of protein synthesis inhibition on proteasome-mediated protein degradation in Caenorhabditis elegans
Åpne denne publikasjonen i ny fane eller vindu >>Study of the effects of protein synthesis inhibition on proteasome-mediated protein degradation in Caenorhabditis elegans
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-80902 (URN)
Tilgjengelig fra: 2020-03-30 Laget: 2020-03-30 Sist oppdatert: 2020-03-30bibliografisk kontrollert
4. Study of the effects of increased proteasome-mediated proteolysis on protein synthesis rate
Åpne denne publikasjonen i ny fane eller vindu >>Study of the effects of increased proteasome-mediated proteolysis on protein synthesis rate
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
urn:nbn:se:oru:diva-80903 (URN)
Tilgjengelig fra: 2020-03-30 Laget: 2020-03-30 Sist oppdatert: 2020-03-30bibliografisk kontrollert

Open Access i DiVA

Cover(195 kB)4 nedlastinger
Filinformasjon
Fil COVER01.pdfFilstørrelse 195 kBChecksum SHA-512
317a2a1b4d8632b4da9da73986e63f53f526e9d153f30c06b7415ca38c9033af78ead1a70b0e0d5fff0690528a9979b2263ccac2e1405388098b306a65038e35
Type coverMimetype application/pdf
Functional Analysis of the Proteasome in Eukaryotic Organisms(8317 kB)1 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 8317 kBChecksum SHA-512
1fdc7156361cbb7241436b09f737f6225900c681026a76383f98fc3f19331e04d7a7dfd71600d0fa6d1d2e8afc302c6feda95c15d0a583f5eb65ea112b8726f4
Type fulltextMimetype application/pdf
Spikblad(166 kB)0 nedlastinger
Filinformasjon
Fil SPIKBLAD01.pdfFilstørrelse 166 kBChecksum SHA-512
f14e02f8815fc2e09ca190883ac5e96c828de3c18940959d1577e091226654bbc6f836ce0127702950301c300f032409391e4cd48eb47b18486da882115320a1
Type spikbladMimetype application/pdf

Personposter BETA

Sakellari, Marianthi

Søk i DiVA

Av forfatter/redaktør
Sakellari, Marianthi
Av organisasjonen

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 1 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

isbn
urn-nbn

Altmetric

isbn
urn-nbn
Totalt: 139 treff
12345674 of 16
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf