TY - JOUR
T1 - Graphene quantum dots rescue protein dysregulation of pancreatic β-cells exposed to human islet amyloid polypeptide
AU - Faridi, Ava
AU - Sun, Yunxiang
AU - Mortimer, Monika
AU - Aranha, Ritchlynn R.
AU - Nandakumar, Aparna
AU - Li, Yuhuan
AU - Javed, Ibrahim
AU - Kakinen, Aleksandr
AU - Fan, Qingqing
AU - Purcell, Anthony W.
AU - Davis, Thomas P.
AU - Ding, Feng
AU - Faridi, Pouya
AU - Ke, Pu Chun
PY - 2019/11
Y1 - 2019/11
N2 - The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 diabetes. Human islet amyloid polypeptide (IAPP), co-secreted with insulin by pancreatic β-cells, plays dual roles in both glycemic control and the pathology of type 2 diabetes. While IAPP can activate the NLRP3 inflammasome and modulate cellular autophagy, apoptosis and extracellular matrix metabolism, no data is available concerning intracellular protein expression upon exposure to the polypeptide. More surprisingly, how intracellular protein expression is modulated by nanoparticle inhibitors of protein aggregation remains entirely unknown. In this study, we first examined the changing proteomes of βTC6, a pancreatic β-cell line, upon exposure to monomeric, oligomeric and fibrillar IAPP, and detailed cellular protein expression rescued by graphene quantum dots (GQDs), an IAPP inhibitor. We found that 29 proteins were significantly dysregulated by the IAPP species, while majority of these proteins were nucleotide-binding proteins. Collectively, our liquid chromatography tandem-mass spectrometry, fluorescence quenching, helium ion microscopy, cytotoxicity and discreet molecular dynamics simulations data revealed a remarkable capacity of GQDs in regulating aberrant protein expression through H-bonding and hydrophobic interactions, pointing to nanomedicine as a new frontier against human amyloid diseases. [Figure not available: see fulltext.].
AB - The amyloid aggregation of peptides and proteins is a hallmark of neurological disorders and type 2 diabetes. Human islet amyloid polypeptide (IAPP), co-secreted with insulin by pancreatic β-cells, plays dual roles in both glycemic control and the pathology of type 2 diabetes. While IAPP can activate the NLRP3 inflammasome and modulate cellular autophagy, apoptosis and extracellular matrix metabolism, no data is available concerning intracellular protein expression upon exposure to the polypeptide. More surprisingly, how intracellular protein expression is modulated by nanoparticle inhibitors of protein aggregation remains entirely unknown. In this study, we first examined the changing proteomes of βTC6, a pancreatic β-cell line, upon exposure to monomeric, oligomeric and fibrillar IAPP, and detailed cellular protein expression rescued by graphene quantum dots (GQDs), an IAPP inhibitor. We found that 29 proteins were significantly dysregulated by the IAPP species, while majority of these proteins were nucleotide-binding proteins. Collectively, our liquid chromatography tandem-mass spectrometry, fluorescence quenching, helium ion microscopy, cytotoxicity and discreet molecular dynamics simulations data revealed a remarkable capacity of GQDs in regulating aberrant protein expression through H-bonding and hydrophobic interactions, pointing to nanomedicine as a new frontier against human amyloid diseases. [Figure not available: see fulltext.].
KW - amyloid
KW - graphene quantum dot
KW - islet amyloid polypeptide (IAPP)
KW - oligomer
KW - protein expression
UR - http://www.scopus.com/inward/record.url?scp=85074028721&partnerID=8YFLogxK
U2 - 10.1007/s12274-019-2520-7
DO - 10.1007/s12274-019-2520-7
M3 - Article
AN - SCOPUS:85074028721
VL - 12
SP - 2827
EP - 2834
JO - Nano Research
JF - Nano Research
SN - 1998-0124
IS - 11
ER -