Tat-biliverdin reductase A protects INS-1 cells from human islet amyloid polypeptide-induced cytotoxicity by alleviating oxidative stress and ER stress

2017 ◽  
Vol 41 (5) ◽  
pp. 514-524 ◽  
Author(s):  
Su Jin Lee ◽  
Hyung Kyung Kang ◽  
Won Sik Eum ◽  
Jinseu Park ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Biliverdin Reductase ◽  
Human Islet Amyloid Polypeptide

scholarly journals His18 promotes reactive oxidative stress production in copper-ion mediated human islet amyloid polypeptide aggregation

RSC Advances ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 5566-5571
Author(s):  
Gengyang Huo ◽  
Wenyong Chen ◽  
Jianhua Wang ◽  
Xinxing Chu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Islet Amyloid Polypeptide ◽  
Copper Ion ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

His18 promotes H2O2 production in copper-ion mediated hIAPP aggregation.

scholarly journals FoxA2 and RNA Pol II Mediate Human Islet Amyloid Polypeptide Turnover in ER-stressed Pancreatic β-cells

2021 ◽  
Author(s):  
Diti Chatterjee Bhowmick ◽  
Lydia Burnett ◽  
Zhanar Kudaibergenova ◽  
Aleksandar Jeremic
Keyword(s):  
Er Stress ◽  
High Glucose ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Β Cells ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Nucleolar Organization ◽  
Insulinoma Cells ◽  
Rat Insulinoma

Here, we investigated transcriptional and trafficking mechanisms of human islet amyloid polypeptide (hIAPP) in normal and stressed β-cells. In high glucose-challenged human islets and rat insulinoma cells overexpressing hIAPP, cell fractionation studies revealed increased accumulation of hIAPP. Unexpectedly, a significant fraction (up to 22%) of hIAPP was found in the nuclear soluble and chromatin-enriched fractions of cultured human islet and rat insulinoma cells. The nucleolar accumulation of monomeric forms of hIAPP did not have any adverse effect on the proliferation of β-cells nor did it affect nucleolar organization or function. However, intact nucleolar organization and function were essential for hIAPP expression under normal and ER-stress conditions as RNA polymerase II inhibitor, α-amanitin, reduced hIAPP protein expression evoked by high glucose and thapsigargin. Promoter activity studies revealed the essential role of transcription factor FoxA2 in hIAPP promoter activation in ER-stressed β-cells. Transcriptome and secretory studies demonstrate that the biosynthetic and secretory capacity of islet β-cells was preserved during ER stress. Thus, the main reason for increased intracellular hIAPP accumulation is its enhanced biosynthesis under these adverse conditions.

Recombinant human islet amyloid polypeptide forms shorter fibrils and mediates β-cell apoptosis via generation of oxidative stress

2017 ◽  
Vol 474 (23) ◽  
pp. 3915-3934 ◽  
Author(s):  
Richa Dubey ◽  
Pooja Minj ◽  
Nikita Malik ◽  
Devika M. Sardesai ◽  
Shruti H. Kulkarni ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Protein Misfolding ◽  
Comprehensive Evaluation ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Β Cell ◽  
Islet Amyloid ◽  
Isolated Pancreatic Islets ◽  
Human Islet Amyloid Polypeptide

Protein misfolding and aggregation play an important role in many human diseases including Alzheimer's, Parkinson's and type 2 diabetes mellitus (T2DM). The human islet amyloid polypeptide (hIAPP) forms amyloid plaques in the pancreas of T2DM subjects (>95%) that are involved in deteriorating islet function and in mediating β-cell apoptosis. However, the detailed mechanism of action, structure and nature of toxic hIAPP species responsible for this effect remains elusive to date mainly due to the high cost associated with the chemical synthesis of pure peptide required for these studies. In the present work, we attempted to obtain structural and mechanistic insights into the hIAPP aggregation process using recombinant hIAPP (rhIAPP) isolated from Escherichia coli. Results from biophysical and structural studies indicate that the rhIAPP self-assembled into highly pure, β-sheet-rich amyloid fibrils with uniform morphology. rhIAPP-mediated apoptosis in INS-1E cells was associated with increased oxidative stress and changes in mitochondrial membrane potential. The transcript levels of apoptotic genes - Caspase-3 and Bax were found to be up-regulated, while the levels of the anti-apoptotic gene - Bcl2 were down-regulated in rhIAPP-treated cells. Additionally, the expression levels of genes involved in combating oxidative stress namely Catalase, SOD1 and GPx were down-regulated. rhIAPP exposure also affected glucose-stimulated insulin secretion from isolated pancreatic islets. The aggregation of rhIAPP also occurred significantly faster when compared with that of the chemically synthesized peptide. We also show that the rhIAPP fibrils were shorter and more cytotoxic. In summary, our study is one among the few to provide comprehensive evaluation of structural, biophysical and cytotoxic properties of rhIAPP.

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans

Diabetes ◽  
1994 ◽  
Vol 43 (5) ◽  
pp. 640-644 ◽  
Author(s):  
E. J. de Koning ◽  
J. W. Hoppener ◽  
J. S. Verbeek ◽  
C. Oosterwijk ◽  
K. L. van Hulst ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals The flanking peptides issue from the maturation of the human islet amyloid polypeptide (hIAPP) slightly modulate hIAPP-fibril formation but not hIAPP-induced cell death

Biochimie ◽  
2020 ◽  
Vol 170 ◽  
pp. 26-35 ◽  
Author(s):  
Shadai Salazar Vazquez ◽  
Bertrand Blondeau ◽  
Pierre Cattan ◽  
Mathieu Armanet ◽  
Ghislaine Guillemain ◽  
...  
Keyword(s):  
Cell Death ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals Regulation of divalent metal ions to the aggregation and membrane damage of human islet amyloid polypeptide oligomers

RSC Advances ◽  
2021 ◽  
Vol 11 (21) ◽  
pp. 12815-12825
Author(s):  
Yajie Wang ◽  
Feihong Meng ◽  
Tong Lu ◽  
Chunyun Wang ◽  
Fei Li
Keyword(s):  
Metal Ions ◽  
Metal Binding ◽  
Membrane Damage ◽  
Islet Amyloid Polypeptide ◽  
Divalent Metal ◽  
Human Islet ◽  
Divalent Metal Ions ◽  
Islet Amyloid ◽  
Induced Membrane ◽  
Human Islet Amyloid Polypeptide

Their is a counteraction between a decrease in the disruptive ability of metal-associated oligomer species and an increase in the quantity of oligomers promoted by the metal binding in the activity of hIAPP induced membrane damage.

scholarly journals Interactions of human islet amyloid polypeptide with lipid structure of different curvatures

2020 ◽  
Vol 10 (6) ◽  
pp. 412-418
Author(s):  
Le Mei ◽  
Wenhui Shen ◽  
Xuwei Wu ◽  
Jie Liu ◽  
Dechang Li ◽  
...  
Keyword(s):  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Lipid Structure ◽  
Human Islet Amyloid Polypeptide

scholarly journals Amyloidogenicity and Cytotoxicity of Recombinant Mature Human Islet Amyloid Polypeptide (rhIAPP)

2004 ◽  
Vol 279 (41) ◽  
pp. 42803-42810 ◽  
Author(s):  
Dahabada H. J. Lopes ◽  
Christian Colin ◽  
Theri L. Degaki ◽  
Ana Christina V. de Sousa ◽  
Marcelo N. N. Vieira ◽  
...  
Keyword(s):  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide
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