Novel insight into streptozotocin-induced diabetic rats from the protein misfolding perspective
Por:
Leyva-Garcia, Edgar, Lara-Martinez, Reyna, Moran-Zanabria, Liborio, Revilla-Monsalve, Cristina, Felipe Jimenez-Garcia, Luis, Oviedo, Norma, Murata, Chiharu, Garrido-Magana, Eulalia, Altamirano-Bustamante, Nelly F., Altamirano-Bustamante, Myriam M.
Publicada:
14 sep 2017
Categoría:
Multidisciplinary
Resumen:
Protein folding is a process of self-assembly defined by the sequence of
the amino acids of the protein involved. Additionally, proteins tend to
unfold, misfold and aggregate due to both intrinsic and extrinsic
causes. Human islet amyloid polypeptide (hIAPP) aggregation is an early
step in diabetes mellitus. However, the aggregation of rat IAPP (rIAPP)
remains an open question. Adult female Sprague-Dawley rats weighing
150-250 g were divided into two groups. The experimental group
(streptozotocin [STZ]) (n = 21) received an intraperitoneal injection
of a single dose of 40 mg/kg STZ. We used the mouse anti-IAPP antibody
and the anti-amyloid oligomer antibody to study the temporal course of
rIAPP oligomerization during STZ-induced diabetes using a wide array of
methods, strategies and ideas derived from biochemistry, cell biology,
and proteomic medicine. Here, we demonstrated the tendency of rIAPP to
aggregate and trigger cooperative processes of self-association or
hetero-assembly that lead to the formation of amyloid oligomers (trimers
and hexamers). Our results are the first to demonstrate the role of
rIAPP amyloid oligomers in the development of STZ-induced diabetes in
rats. The IAPP amyloid oligomers are biomarkers of the onset and
progression of diabetes and could play a role as therapeutic targets.
Filiaciones:
Leyva-Garcia, Edgar:
Inst Mexicano Seguro Social, Unidad Invest Enfermedades Metab, Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico
Lara-Martinez, Reyna:
Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City, DF, Mexico
Moran-Zanabria, Liborio:
Inst Mexicano Seguro Social, Unidad Invest Enfermedades Metab, Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico
Revilla-Monsalve, Cristina:
Inst Mexicano Seguro Social, Unidad Invest Enfermedades Metab, Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico
Felipe Jimenez-Garcia, Luis:
Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City, DF, Mexico
Oviedo, Norma:
Inst Mexicano Seguro Social, Ctr Med Nacl La Raza, Unidad Invest Inmunol & Infectol, Mexico City, DF, Mexico
Murata, Chiharu:
Inst Nacl Pediat, Mexico City, DF, Mexico
Garrido-Magana, Eulalia:
UMAE Hosp Pediat, Ctr Med Nacl Siglo XXI, Serv Endocrinol, IMSS, Mexico City, DF, Mexico
Altamirano-Bustamante, Nelly F.:
Inst Nacl Pediat, Mexico City, DF, Mexico
Altamirano-Bustamante, Myriam M.:
Inst Mexicano Seguro Social, Unidad Invest Enfermedades Metab, Ctr Med Nacl Siglo XXI, Mexico City, DF, Mexico
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