Dataset Information

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT₁-PGC_1a energy metabolism pathway.

ABSTRACT: A large number of data suggest that caloric restriction (CR) has a protective effect on myocardial ischemia/reperfusion injury (I/R) in the elderly. However, the mechanism is still unclear. In this study, we created the I/R model in vivo by ligating the mice left coronary artery for 45 min followed by reperfusion. C57BL/6J wild-type mice were randomly divided into a young group fed ad libitum (y-AL), aged fed ad libitum (a-AL) and aged calorie restriction group (a-CR, 70% diet restriction), and fed for 6 weeks. The area of myocardial infarction was measured by Evan's blue-TTC staining, plasma cholesterol content quantified by ELISA, fatty acids and glucose measured by Langendorff working system, as well as protein expression of AMPK/SIRT₁/PGC_1a signaling pathway related factors in myocardial tissue detected by immunoblotting. Our results showed that CR significantly reduced infarct size in elderly mice after I/R injury, promoted glycolysis regardless of I/R injury, and restored myocardial glucose uptake in elderly mice. Compared with a-AL group, CR significantly promoted the expression of p-AMPK, SIRT₁, p-PGC_1a, and SOD₂, but decreased PPARγ expression in aged mice. In conclusion, our results suggest that CR protects elderly mice from I/R injury by altering myocardial substrate energy metabolism via the AMPK/SIRT₁/PGC_1a pathway.

SUBMITTER: Guo Z

PROVIDER: S-EPMC9899227 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT<sub>1</sub>-PGC<sub>1a</sub> energy metabolism pathway.

Guo Zhijia Z Wang Meng M Ying Xiaodong X Yuan Jiyu J Wang Chenggang C Zhang Wenjie W Tian Shouyuan S Yan Xiaoyan X

Scientific reports 20230204 1

A large number of data suggest that caloric restriction (CR) has a protective effect on myocardial ischemia/reperfusion injury (I/R) in the elderly. However, the mechanism is still unclear. In this study, we created the I/R model in vivo by ligating the mice left coronary artery for 45 min followed by reperfusion. C57BL/6J wild-type mice were randomly divided into a young group fed ad libitum (y-AL), aged fed ad libitum (a-AL) and aged calorie restriction group (a-CR, 70% diet restriction), and ...[more]

PMID: 36739302

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Project description:BackgroundTo study the protective effects of delayed remote ischemic preconditioning (RIPC) against spinal cord ischemia-reperfusion injury (SCIRI) in mice and determine whether SIRT3 is involved in this protection and portrayed its upstream regulatory mechanisms.MethodsIn vivo, WT or SIRT3 global knockout (KO) mice were exposed to right upper and lower limbs RIPC or sham ischemia. After 24 h, the abdominal aorta was clamped for 20 min, then re-perfused for 3 days. The motor function of mice, number of Nissl bodies, apoptotic rate of neurons, and related indexes of oxidative stress in the spinal cord were measured to evaluate for neuroprotective effects. The expression and correlation of SIRT3 and NMDAR were detected by WB and immunofluorescence. In vitro, primary neurons were exacted and OGD/R was performed to simulate SCIRI in vivo. Neuronal damage was assessed by observing neuron morphology, detecting LDH release ratio, and flow cytometry to analyze the apoptosis. MnSOD and CAT enzyme activities, GSH and ROS level were also measured to assess neuronal antioxidant capacity. NMDAR-AMPK-PGC-1α signaling was detected by WB to portray upstream regulatory mechanisms of RIPC regulating SIRT3.ResultsCompared to the SCIRI mice without RIPC, mice with RIPC displayed improved motor function recovery, a reduced neuronal loss, and enhanced antioxidant capacity. To the contrary, the KO mice did not exhibit any effect of RIPC-induced neuroprotection. Similar results were observed in vitro. Further analyses with spinal cord tissues or primary neurons detected enhanced MnSOD and CAT activities, as well as increased GSH level but decreased MDA or ROS production in the RIPC + I/R mice or NMDA + OGD/R neurons. However, these changes were completely inhibited by the absence of SIRT3. Additionally, NMDAR-AMPK-PGC-1α signaling was activated to upregulate SIRT3 levels, which is essential for RIPC-mediated neuroprotection.ConclusionsRIPC enhances spinal cord ischemia tolerance in a SIRT3-dependent manner, and its induced elevated SIRT3 levels are mediated by the NMDAR-AMPK-PGC-1α signaling pathway. Combined therapy targeting SIRT3 is a promising direction for treating SCIRI.

Dataset Information

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT₁-PGC_1a energy metabolism pathway.

Publications

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT<sub>1</sub>-PGC<sub>1a</sub> energy metabolism pathway.

Similar Datasets

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Dataset Information

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT1-PGC1a energy metabolism pathway.

Publications

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT<sub>1</sub>-PGC<sub>1a</sub> energy metabolism pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Caloric restriction increases the resistance of aged heart to myocardial ischemia/reperfusion injury via modulating AMPK-SIRT₁-PGC_1a energy metabolism pathway.