Catalase inhibition in diabetic rats potentiates DNA damage and apoptotic cell death setting the stage for cardiomyopathy
2014
Аутори:
Ivanović Matić, SvetlanaBogojević, Desanka
Martinović, Vesna
Petrovic, Anja
Jovanovic-Stojanov, Sofija
Poznanović, Goran
Grigorov, Ilijana
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Diabetes is a risk factor for cardiovascular disease that has a
multifactorial etiology, with oxidative stress as an important
component. Our previous observation of a significant diabetes-related
increase in rat cardiac catalase (CAT) activity suggested that CAT could
play a major role in delaying the development of diabetic
cardiomyopathy. Thus, in the present work, we examined the effects of
the daily administration of the CAT inhibitor, 3-amino-1,2,4-triazole (1
mg/g), on the hearts of streptozotocin (STZ)-induced diabetic rats.
Administration of CAT inhibitor was started from the 15th day after the
last STZ treatment (40 mg/kg/5 days), and maintained until the end of
the 4th or 6th weeks of diabetes. Compared to untreated diabetic rats,
at the end of the observation period, CAT inhibition lowered the induced
level of cardiac CAT activity to the basal level and decreased CAT
protein expression, mediated through a decline in the nuclear factor
erythroid-derived 2-like 2 /nuclear factor-kappa B p65 (Nrf2/NF-kappa B
p65) subunit ratio. The perturbed antioxidant defenses resulting from
CAT inhibition promoted increased H2O2 production (P < 0.05) and lipid
peroxidation (P < 0.05). Generated cytotoxic stimuli increased DNA
damage (P < 0.05) and activated pro-apoptotic events, observed as a
decrease (P < 0.05) in the ratio of the apoptosis regulator proteins
Bcl-2/Bax, increased (P < 0.05) presence of the poly(ADP-ribose)
polymerase-1 (PARP-1) 85 kDa apoptotic fragment and cytoplasmic levels
of cytochrome C. These findings confirm an important function of CAT in
the suppression of events leading to diabetes-promoted cardiac
dysfunction and cardiomyopathy.
Кључне речи:
3-amino-1,2,4-triazole; Apoptotic pathways; Catalase; Diabetic cardiomyopathy; Nrf2/NF-kappa B p65 signalingИзвор:
Journal of Physiology and Biochemistry, 2014, 70, 4, 947-959
DOI: 10.1007/s13105-014-0363-y
ISSN: 1877-8755