Mahmoud, B. (2021) A-kinase interacting protein 1 attenuates mitochondrial respiratory function in hearts of mice subjected to exercise. thesis, Medicine.
Full text available on request.Abstract
Introduction: Heart failure (HF) is a pandemic associated with poor prognosis. To this day, no cure has been found. Studying physiological cardiac growth can provide insights that could be applied to HF. A kinase interacting protein 1 (AKIP1) is believed to contribute to physiological hypertrophy by affecting the mitochondria. However, in vivo studies on this topic are lacking. Objective: To assess the effects of AKIP1 on mitochondrial function, defined as state 3 respiration, and mitochondrial dynamics in exercise-induced cardiac hypertrophy. Methods: Male, 8-12 weeks old, wildtype (WT) and AKIP1 transgenic (AKIP1- TG) mice containing an overexpression of AKIP1 in cardiomyocytes were subjected to either voluntary wheel running exercise or sedentary conditions for four weeks, n=16-17 per group. Body weight, heart weight/tibia length (HW/TL) and running distances were measured. Mitochondrial function was analyzed using respirometry. Biochemical assays focusing on biogenesis, mitophagy and fusion were performed to assess mitochondrial dynamics. Oneway ANOVA was used for statistical analysis. Results: HW/TL was increased in AKIP1-TG running mice (p=0.015), without significant differences in running performance. Furthermore, AKIP1-TG mice had reduced state 3 respiration rates vs. WT mice, both at baseline and after exercise, with running group means of 350.8 ± 62.1 vs. 482.7 ± 40.9 nmol/min/mg protein; p=0.002 for glucose metabolism, with similar reductions observed in fatty acid metabolism (p=0.003). Additionally, western blots showed higher expressions of autophagy marker p62 and biogenesis marker PGC1a in AKIP1-TG mice, especially after exercise (p=0.028; p=0.058). Conclusion: AKIP1 augments cardiac growth after exercise but, contrary to in vitro studies, attenuates mitochondrial respiratory function. Additionally, AKIP1 may affect mitochondrial dynamics, but the exact mechanisms are not clarified yet.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Westenbrink, dr. B.D. |
| Faculty: | Medical Sciences |
| Date Deposited: | 03 Jan 2022 11:01 |
| Last Modified: | 03 Jan 2022 11:01 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2921 |
Actions (login required)
 |
View Item |