Akademik Veri Yönetim Sistemi
Yeşilkaya A. (Yürütücü), Kırça M.
TÜBİTAK Projesi, 2018 - 2019
Methylglyoxal (MGO) is considered responsible for the
detrimental effects of high blood glucose. MGO is produced as a by-product of
the glycolysis pathway. While the glyoxalase system removes it, the system
fails in people with diabetes. MGO concentration is detected as elevated in
these patients. Endoplasmic reticulum (ER) stress may play a role in
atherosclerosis progression and vascular diseases. If ER stress persists, it
may result in apoptosis of the cell. As a result, stabilized plaque structure
by these cells may be ruptured and cause a stroke. This study aimed to
investigate whether MGO can induce ER stress and apoptosis in vascular smooth
muscle cells (VSMCs). Also, the effects of aminogua- nidine hydrochloride
(AGH), 4-phenylbutyric acid (4-PBA), and tauroursodeoxycholic acid (TUDCA) were
scrutinized to relieve ER stress. VSMCs were isolated from rat aorta and
cultured primary. PERK phos- phorylation, IRE1a, ATF6, BiP (Grp78), and CHOP
expressions were detected by the western blot tech- nique. A caspase-3 assay
kit measured the apoptosis. MGO could stimulate the main three ER stress
pathways, PERK phosphorylation, IRE1a, and ATF6 expressions in a time- and
concentration-dependent manner. Furthermore, AGH, 4-PBA, and TUDCA alleviated
MGO-induced ER stress. However, we detected neither an increase in CHOP
expression nor apoptosis in VSMCs. This study shows that MGO induces ER stress
even at low concentrations in VSMCs. The impaired glyoxalase system may cause
MGO accumulation and result in persisted ER stress. Supposing that ER stress is
not mitigated, this table might be finalized in cell apoptosis, plaque rupture,
and stroke.