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Published on: January 18, 2019
Sestrin2 serves as a scaffold protein to maintain cardiac energy and metabolic homeostasis during pathological stress
Blaise Seale1, Lily Slotabec1,2, Jennie D Nguyen1
1Department of Physiology and Biophysics, Mississippi Center for Heart Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Insights
Sestrin2 (Sesn2) protein protects heart health by managing metabolic balance and stress responses. Understanding Sesn2 pathways offers new therapeutic targets for cardiovascular diseases (CVDs) and metabolic disorders.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Cardiovascular diseases (CVDs) are a major global health burden, often exacerbated by metabolic dysfunction and cellular stress.
- Sestrin2 (Sesn2) is a key stress-inducible protein that plays a vital role in maintaining cardiac metabolic homeostasis.
- Pathological conditions frequently involve metabolic imbalances and increased cellular stress, contributing to CVD morbidity and mortality.
Purpose of the Study:
- To review the multifaceted mechanisms by which Sestrin2 (Sesn2) regulates cellular pathways crucial for cardiac health.
- To explore the role of Sesn2 in response to various stressors, including oxidative stress, hypoxia, and energy depletion.
- To identify potential therapeutic strategies for CVDs and metabolic disorders by elucidating Sesn2-mediated cellular processes.
Main Methods:
- Literature review focusing on Sestrin2 (Sesn2) function in cellular stress response and metabolism.
- Analysis of key signaling pathways regulated by Sesn2, such as AMPK-mTORC1, Sesn2-Nrf2, and HIF1α-Sesn2.
- Examination of Sesn2's role in enhancing antioxidant defenses, promoting autophagy, and modulating inflammation.
Main Results:
- Sestrin2 (Sesn2) is upregulated by diverse cellular stressors, indicating its protective role under pathological conditions.
- Sesn2 modulates critical pathways including AMPK-mTORC1, Sesn2-Nrf2, and HIF1α-Sesn2 to maintain cellular and metabolic balance.
- Sesn2 enhances antioxidant capacity, facilitates autophagy, and exerts anti-inflammatory effects, all contributing to cardiac resilience.
Conclusions:
- Sestrin2 (Sesn2) is a pivotal regulator of cellular responses to metabolic and oxidative stress in the heart.
- Understanding the intricate mechanisms of Sesn2 offers significant potential for developing novel therapeutics for cardiovascular diseases.
- Targeting Sesn2 pathways presents a promising strategy to improve cardiac health and combat metabolic disorders.
Abstract:
Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality worldwide. Metabolic imbalances and pathological stress often contribute to increased mortality. Sestrin2 (Sesn2) is a stress-inducible protein crucial in maintaining cardiac energy and metabolic homeostasis under pathological conditions. Sesn2 is upregulated in response to various stressors, including oxidative stress, hypoxia, and energy depletion, and mediates multiple cellular pathways to enhance antioxidant defenses, promote autophagy, and inhibit inflammation. This review explores the mechanisms through which Sesn2 regulates these pathways, focusing on the AMPK-mTORC1, Sesn2-Nrf2, and HIF1α-Sesn2 pathways, among others. We can identify the potential therapeutic targets for treating CVDs and related metabolic disorders by comprehending these complex mechanisms. Sesn2's unique ability to respond thoroughly to metabolic challenges, oxidative stress, and inflammation makes it a promising prospect for enhancing cardiac health and resilience against pathological stress.
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