Abstract
Background
Cardiac apoptosis plays a key role in increased morbidity associated with aging-induced-cardiac disorder. Mitochondria play an important role in cardiac apoptosis, and dynamin-related protein 1 (Drp1), as a main mediator of mitochondrial fission, can trigger the mitophagy process to sustain the mitochondrial quality. The present study was done to determine the effect of vitamin D (VitD) treatment on cardiac hypertrophy through mitophagy regulation in aged animals induced by D-galactose (D-GAL).
Methods and results
Male Wistar rats were randomly divided into four groups: control, D-GAL (aging group), D-GAL co-injected with VitD (D-GAL ± VitD), and D-GAL plus ethanol (D-GAL ± Ethanol). Aging was induced by an intraperitoneal (i.p.) administration of D-GAL at 150 mg/kg daily for eight weeks and also VitD (400 IU/kg) or ethanol was injected (i.p.) into aging rats. Then, the levels of cardiac mitophagy and cardiac apoptosis were determined by measuring the expression of tensin homologue (PTEN)-induced putative kinase 1 (PINK1), Drp1, Bcl2-Associated X (Bax), and B-cell lymphoma 2 (Bcl2) genes. Aging in rats was associated with a reduction in mitophagy and also an increase in apoptosis of the heart through down-regulation of Drp1, PINK1, and Bcl2 genes and also up-regulation of Bax. However, VitD improved cardiac hypertrophy through cardiac mitophagy in D-GAL-induced aging rats.
Conclusion
VitD can inhibit cardiac hypertrophy by an increase in mitophagy and a decrease in apoptosis in the aging heart.
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Data Availability
The data used and analyzed in this study are available from the Corresponding author upon reasonable request.
Abbreviations
- ANOVA:
-
Analysis of variance
- Bax :
-
Bcl-2-associated X protein
- Bcl-2 :
-
B-cell lymphoma 2
- BW:
-
Body Weight
- CH:
-
Cardiac hypertrophy
- D-GAL:
-
D-galactose
- Drp1 :
-
Dynamin-related protein 1
- HW:
-
Heart Weight
- i.p.:
-
Intraperitoneally
- PINK1 :
-
tensin homologue (PTEN)-induced putative kinase 1
- QRT-PCR:
-
Quantitative Real-Time PCR
- ROS:
-
Reactive oxygen species
- SE:
-
Standard error
- VitD:
-
Vitamin D
- VDR:
-
VitD receptor
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Acknowledgements
The authors would like to thank and appreciate the Hamadan University of Medical Sciences for funding the present research.
Funding
This study was funded by the Vice-Chancellor for Research and Technology, Hamadan University of Medical Sciences (No. 140005124073).
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SSh and KHR-A contributed to data collection and interpretation and wrote the manuscript. AK performed the experiments and provided reagents.IS conceived and designed the experiments.SH provided reagents and materials and analyzed the data. SSA and PH contributed to data collection and analysis.FR-A designed the study, contributed to data collection and interpretation, and wrote the manuscript.
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Shahidi, S., Ramezani-Aliakbari, K., Komaki, A. et al. Effect of vitamin D on cardiac hypertrophy in D-galactose-induced aging model through cardiac mitophagy. Mol Biol Rep 50, 10147–10155 (2023). https://doi.org/10.1007/s11033-023-08875-7
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DOI: https://doi.org/10.1007/s11033-023-08875-7