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Dynamics of mitochondrial function changes in the cerebral vasculature of type 2 diabetic rats
Author(s) -
Merdzo Ivan,
Rutkai Ibolya,
Sure Venkata N. L. R.,
McNulty Catherine A.,
Katakam Prasad V.,
Busija David W.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1015.22
Subject(s) - medicine , endocrinology , chemistry , mitochondrion , type 2 diabetes , basal (medicine) , respiration , cerebral arteries , insulin , diabetes mellitus , anatomy , biochemistry
Mitochondrial dysfunction has been suggested as a potential underlying cause of pathological conditions associated with type 2 diabetes (T2DM). We have previously shown that mitochondrial respiration levels assessed by the Seahorse XFe24 analyzer in large cerebral arteries, and mitochondrial protein levels measured by western blot in cerebral arteries and microvessels, were similar in insulin resistant, non‐diabetic, Zucker obese rats and lean control rats ( Am J Physiol 310:H830‐838, 2016). In the present study we extended our investigations into mitochondrial dynamics and superoxide production of the cerebral vasculature of 14 week old Zucker diabetic fatty obese rats (ZDFO) with early T2DM. Body weight and blood glucose levels were significantly higher in the ZDFO compared to the control, lean (ZDFL) rats (347.2 ± 10.18 g vs. 320.4 ± 3.9 g, n = 20, P < 0.05; and 26.33 ± 1.56 mmol/L vs. 9.18 ± 0.46 mmol/L, n = 20, P < 0.05; respectively). In addition, basal mitochondrial respiration and proton leak were significantly decreased in the large cerebral arteries of the ZDFO rats compared with ZDFL (181.4 ± 10.93 pM/min/μg protein vs. 129.7 ± 8.211 pM/min/μg protein, n = 59, P < 0.05; and 149.3 ± 10.41 pM/min/μg protein vs. 100.3 ± 7.56 pM/min/μg protein, n = 59, P < 0.05; respectively). Furthermore, superoxide production was significantly increased in the microvessels of the ZDFO group (2355 ± 628 vs. 208 ± 48, n = 10, P < 0.05). The expression of mitochondrial proteins total MnSOD and VDAC were significantly lower in the cerebral microvessels (90.35 ± 9.13% vs. 123.1 ± 12.77%, n = 13, P < 0.05; and 23.63 ± 2.62% vs. 30.54 ± 2.07%, n = 12, P < 0.05; respectively), and levels the acetylated or active form of MnSOD were significantly reduced in large arteries of ZDFO group (89.72 ± 3.17% vs. 52.23 ± 6.01%, n = 12, P < 0.05). Despite evidence of increased oxidative stress in ZDFO, exogenous superoxide dismutase was not able to restore mitochondrial respiration in ZDFO rats. Our results show for the first time that mitochondria of large arteries and microvessels are adversely affected in the cerebral vasculature during the early stages of T2DM. Support or Funding Information This work was supported by National Institutes of Health grants (DWB: HL‐077731and HL093554), Louisiana Board of Regents Support Fund‐Research Competitiveness Subprogram (PVK: LEQSF(2014‐17)‐RD‐A‐11), American Heart Association National Center NRCP Scientist Development Grant (PVK: 14SDG20490359), and American Heart Association Post‐Doctoral Fellowship Grant (IR: 15POST23040005). This research was also supported by the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program (DWB).