The redox environment triggers conformational changes and
aggregation of hIAPP in Type II Diabetes

J 2017

The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes

CAMARGO, D.C.R.; Konstantinos TRIPSIANES; K. BUDAY; A. FRANKO; C. GOBL et al.

Základní údaje

Originální název

The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes

Autoři

Vydání

Scientific reports, LONDON, NATURE PUBLISHING GROUP, 2017, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.122

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/17:00100109

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

ISLET AMYLOID POLYPEPTIDE; ENDOPLASMIC-RETICULUM STRESS; DISULFIDE-BOND FORMATION; PANCREATIC BETA-CELLS; HUMAN AMYLIN; HUMAN-IAPP; INSULIN; PROTEINS; NMR; GLUTATHIONE

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 13. 3. 2018 12:20, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents. Aggregation thus induces redox balancing which can assist initially to counteract ER stress. Failure of the protein degradation machinery might finally result in beta-cell disruption and cell death. We further present a structural characterization of hIAPP in solution, demonstrating that the N-terminus of the oxidized peptide has a high propensity to form an alpha-helical structure which is lacking in the reduced state of hIAPP. In healthy cells, this residual structure prevents the conversion into amyloidogenic aggregates.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

Citovat

CAMARGO, D.C.R.; Konstantinos TRIPSIANES; K. BUDAY; A. FRANKO; C. GOBL; C. HARTLMULLER; R. SARKAR; M. AICHLER; G. METTENLEITER; M. SCHULZ; A. BODDRICH; C. ERCK; H. MARTENS; A.K. WALCH; T. MADL; E.E. WANKER; M. CONRAD; M.H. DE ANGELIS a B. REIF. The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes. Scientific reports. LONDON: NATURE PUBLISHING GROUP, 2017, roč. 7, MAR, s. 44041-44051. ISSN 2045-2322. Dostupné z: https://doi.org/10.1038/srep44041.

@article{1409390,
   author = {Camargo, D.C.R. and Tripsianes, Konstantinos and Buday, K. and Franko, A. and Gobl, C. and Hartlmuller, C. and Sarkar, R. and Aichler, M. and Mettenleiter, G. and Schulz, M. and Boddrich, A. and Erck, C. and Martens, H. and Walch, A.K. and Madl, T. and Wanker, E.E. and Conrad, M. and de Angelis, M.H. and Reif, B.},
   article_location = {LONDON},
   article_number = {MAR},
   doi = {https://doi.org/10.1038/srep44041},
   keywords = {ISLET AMYLOID POLYPEPTIDE; ENDOPLASMIC-RETICULUM STRESS; DISULFIDE-BOND FORMATION; PANCREATIC BETA-CELLS; HUMAN AMYLIN; HUMAN-IAPP; INSULIN; PROTEINS; NMR; GLUTATHIONE},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific reports},
   title = {The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes},
   url = {https://www.nature.com/articles/srep44041.pdf},
   volume = {7},
   year = {2017}
}

TY  - JOUR
ID  - 1409390
AU  - Camargo, D.C.R. - Tripsianes, Konstantinos - Buday, K. - Franko, A. - Gobl, C. - Hartlmuller, C. - Sarkar, R. - Aichler, M. - Mettenleiter, G. - Schulz, M. - Boddrich, A. - Erck, C. - Martens, H. - Walch, A.K. - Madl, T. - Wanker, E.E. - Conrad, M. - de Angelis, M.H. - Reif, B.
PY  - 2017
TI  - The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes
JF  - Scientific reports
VL  - 7
IS  - MAR
SP  - 44041
EP  - 44041
PB  - NATURE PUBLISHING GROUP
SN  - 20452322
KW  - ISLET AMYLOID POLYPEPTIDE
KW  - ENDOPLASMIC-RETICULUM STRESS
KW  - DISULFIDE-BOND FORMATION
KW  - PANCREATIC BETA-CELLS
KW  - HUMAN AMYLIN
KW  - HUMAN-IAPP
KW  - INSULIN
KW  - PROTEINS
KW  - NMR
KW  - GLUTATHIONE
UR  - https://www.nature.com/articles/srep44041.pdf
L2  - https://www.nature.com/articles/srep44041.pdf
N2  - Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents. Aggregation thus induces redox balancing which can assist initially to counteract ER stress. Failure of the protein degradation machinery might finally result in beta-cell disruption and cell death. We further present a structural characterization of hIAPP in solution, demonstrating that the N-terminus of the oxidized peptide has a high propensity to form an alpha-helical structure which is lacking in the reduced state of hIAPP. In healthy cells, this residual structure prevents the conversion into amyloidogenic aggregates.
ER  -

CAMARGO, D.C.R.; Konstantinos TRIPSIANES; K. BUDAY; A. FRANKO; C. GOBL; C. HARTLMULLER; R. SARKAR; M. AICHLER; G. METTENLEITER; M. SCHULZ; A. BODDRICH; C. ERCK; H. MARTENS; A.K. WALCH; T. MADL; E.E. WANKER; M. CONRAD; M.H. DE ANGELIS a B. REIF. The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes. \textit{Scientific reports}. LONDON: NATURE PUBLISHING GROUP, 2017, roč.~7, MAR, s.~44041-44051. ISSN~2045-2322. Dostupné z: https://doi.org/10.1038/srep44041.

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