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AMP-Activated Protein Kinases in Health and Disease
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AMP-Activated Protein Kinases in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 May 2024) | Viewed by 7160

Special Issue Editor

Dr. Jinbong Park

E-Mail Website
Guest Editor
College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Soeul 02447, Republic of Korea
Interests: obesity; high-fat diet; brown adipocytes; AMP-activated protein kinase; adipogenesis; thermogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

AMP-activated protein kinase (AMPK) plays an important role in several molecular mechanisms and physiological conditions. AMPK has also been identified in multiple catabolic and anabolic signaling pathways; thus, it is a key enzyme which regulates cellular energy homeostasis, glucose, fatty acid uptake and oxidation. Notably, several diseases are known to be closely related to AMPK levels, including inflammation, cancer and cardiovascular and metabolic diseases. The underlying mechanisms of AMPK in such diseases largely involve a reduction in oxidative stress and inflammatory responses. The functions of AMPK in health and disease are intriguing but still require further research. Recent advances in AMPK research have demonstrated its potential benefits as a target for pharmacological interventions for several diseases.

This Special Issue, entitled “AMP-Activated Protein Kinases in Health and Disease”, welcomes original investigations and comprehensive reviews demonstrating new and advanced research viewpoints on the therapeutic potential of targeting AMPK in maintaining health and treating various diseases.

Dr. Jinbong Park
Guest Editor

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Keywords

  • AMPK
  • inflammation
  • cancer
  • cardiovascular diseases
  • metabolic diseases
  • oxidative stress
  • phytochemicals

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Published Papers (5 papers)

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Research

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10 pages, 3319 KiB  
Article
Involvement of the AMPK Pathways in Muscle Development Disparities Across Genders in Muscovy Ducks
by Wanxin Zhao, Yulin He, Ziyuan Du, Xuanci Yu, Juan Chen, Ang Li and Caiyun Huang
Int. J. Mol. Sci. 2024, 25(18), 10132; https://doi.org/10.3390/ijms251810132 (registering DOI) - 21 Sep 2024
Viewed by 163
Abstract
The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences [...] Read more.
The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits (P < 0.05). Compared to male ducks, the level of serum testosterone in female ducks was decreased, and the estradiol levels were increased (p < 0.05). The RNA-seq analysis identified 102 upregulated and 49 downregulated differentially expressed genes. KEGG analysis revealed that among the top 10 differentially enriched pathways, the AMPK signaling pathway is closely related to muscle growth and development. Additionally, the mRNA and protein levels of CD36, CPT1A, LPL, and SREBP1 were increased and the P-AMPK protein level decreased in the female ducks compared to the male ducks (p < 0.05). In conclusion, muscle development potential difference between male and female ducks is regulated by sex hormones. This process is likely mediated through the activation of the AMPK pathway. Full article
(This article belongs to the Special Issue AMP-Activated Protein Kinases in Health and Disease)
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21 pages, 4722 KiB  
Article
Hypoxic Cardioprotection by New Antihypertensive Compounds in High Salt-Diet Hypertensive Rats: Glucose Transport Participation and Its Possible Pathway
by Manuel A. Hernández-Serda, Aldo Y. Alarcón-López, Víctor H. Vázquez-Valadez, Paola Briseño-Lugo, Pablo A. Martínez-Soriano, Viridiana Leguízamo, Nalleli Torres, Rodrigo González-Terán, Luis A. Cárdenas-Granados, Fausto Sánchez Muñoz, Emma Rodríguez, Claudia Lerma, Alejandra María Zúñiga Muñoz, Enrique Ángeles and Roxana Carbó
Int. J. Mol. Sci. 2024, 25(16), 8812; https://doi.org/10.3390/ijms25168812 - 13 Aug 2024
Viewed by 1137
Abstract
Hypertension (HP) is a health condition that overloads the heart and increases the risk of heart attack and stroke. In an infarction, the lack of oxygen causes an exclusive use of glycolysis, which becomes a crucial source of ATP for the heart with [...] Read more.
Hypertension (HP) is a health condition that overloads the heart and increases the risk of heart attack and stroke. In an infarction, the lack of oxygen causes an exclusive use of glycolysis, which becomes a crucial source of ATP for the heart with a higher glucose uptake mediated by glucose transporters (GLUTs). Due to the unpleasant effects of antihypertensives, new drugs need to be researched to treat this disease. This study aimed to evaluate the cardioprotective effect of three novel antihypertensive compounds (LQMs, “Laboratorio de Química Medicinal”) synthesized from Changrolin under hypoxic conditions with the participation of two primary cardiac GLUT1 and GLUT4 using a high-salt diet HP model. The model used a diet with 10% salt to increase arterial blood pressure in Wistar rats. In isolated cardiomyocytes from these rats, glucose uptake was measured during hypoxia, evaluating the participation of GLUTs with or without the animals’ previous treatment with LQM312, 319, and 345 compounds. In silico calculations were performed to understand the affinity of the compounds for the trafficking of GLUTs. Results: Control cells do shift to glucose uptake exclusively in hypoxia (from 1.84 ± 0.09 µg/g/h to 2.67 ± 0.1 µg/g/h). Meanwhile, HP does not change its glucose uptake (from 2.38 ± 0.24 µg/g/h to 2.33 ± 0.26 µg/g/h), which is associated with cardiomyocyte damage. The new compounds lowered the systolic blood pressure (from 149 to 120 mmHg), but only LQM312 and LQM319 improved the metabolic state of hypoxic cardiomyocytes mediated by GLUT1 and GLUT4. In silico studies suggested that Captopril and LQM312 may mimic the interaction with the AMPK γ-subunit. Therefore, these compounds could activate AMPK, promoting the GLUT4 trafficking signaling pathway. These compounds are proposed to be cardioprotective during hypoxia under HP. Full article
(This article belongs to the Special Issue AMP-Activated Protein Kinases in Health and Disease)
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25 pages, 3404 KiB  
Article
The polyHIS Tract of Yeast AMPK Coordinates Carbon Metabolism with Iron Availability
by Kobi J. Simpson-Lavy and Martin Kupiec
Int. J. Mol. Sci. 2023, 24(2), 1368; https://doi.org/10.3390/ijms24021368 - 10 Jan 2023
Cited by 4 | Viewed by 1936
Abstract
Energy status in all eukaryotic cells is sensed by AMP-kinases. We have previously found that the poly-histidine tract at the N-terminus of S. cerevisiae AMPK (Snf1) inhibits its function in the presence of glucose via a pH-regulated mechanism. We show here that in [...] Read more.
Energy status in all eukaryotic cells is sensed by AMP-kinases. We have previously found that the poly-histidine tract at the N-terminus of S. cerevisiae AMPK (Snf1) inhibits its function in the presence of glucose via a pH-regulated mechanism. We show here that in the absence of glucose, the poly-histidine tract has a second function, linking together carbon and iron metabolism. Under conditions of iron deprivation, when different iron-intense cellular systems compete for this scarce resource, Snf1 is inhibited. The inhibition is via an interaction of the poly-histidine tract with the low-iron transcription factor Aft1. Aft1 inhibition of Snf1 occurs in the nucleus at the nuclear membrane, and only inhibits nuclear Snf1, without affecting cytosolic Snf1 activities. Thus, the temporal and spatial regulation of Snf1 activity enables a differential response to iron depending upon the type of carbon source. The linkage of nuclear Snf1 activity to iron sufficiency ensures that sufficient clusters are available to support respiratory enzymatic activity and tests mitochondrial competency prior to activation of nuclear Snf1. Full article
(This article belongs to the Special Issue AMP-Activated Protein Kinases in Health and Disease)
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Review

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29 pages, 1934 KiB  
Review
Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer
by Lochana Kovale, Manish Kumar Singh, Joungmok Kim and Joohun Ha
Int. J. Mol. Sci. 2024, 25(16), 8647; https://doi.org/10.3390/ijms25168647 - 8 Aug 2024
Viewed by 692
Abstract
Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit [...] Read more.
Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, as certain cancers tend to depend on autophagy for survival. Autophagy, while crucial for maintaining stemness in cancer stem cells (CSCs), can also serve as a vulnerability in certain contexts, making it a complex target for therapy. Regulators of autophagy like AMPK (5′ adenosine monophosphate-activated protein kinase) also play a crucial role in maintaining CSCs stemness by helping CSCs in metabolic reprogramming in harsh environments. The purpose of this review is to elucidate the interplay between autophagy and AMPK in CSCs, highlighting the challenges in targeting autophagy and discussing therapeutic strategies to overcome these limitations. This review focuses on previous research on autophagy and its regulators in cancer biology, particularly in CSCs, addresses the remaining unanswered questions, and potential targets for therapy are also brought to attention. Full article
(This article belongs to the Special Issue AMP-Activated Protein Kinases in Health and Disease)
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15 pages, 323 KiB  
Review
The Role of Natural Products in the Improvement of Cancer-Associated Cachexia
by Yohan Han, Hyo In Kim and Jinbong Park
Int. J. Mol. Sci. 2023, 24(10), 8772; https://doi.org/10.3390/ijms24108772 - 15 May 2023
Cited by 6 | Viewed by 2130
Abstract
The enormous library of natural products and herbal medicine prescriptions presents endless research avenues. However, the lack of research evidence and trials on cancer-induced cachexia limit the therapeutic potential of natural products. Cancer-induced cachexia is a systemic wasting syndrome characterized by continuous body [...] Read more.
The enormous library of natural products and herbal medicine prescriptions presents endless research avenues. However, the lack of research evidence and trials on cancer-induced cachexia limit the therapeutic potential of natural products. Cancer-induced cachexia is a systemic wasting syndrome characterized by continuous body weight loss with skeletal muscle and adipose tissue atrophy. Cancer cachexia is a problem in itself and reduces the quality of life by lessening the treatment efficacy of anticancer drugs. This review summarizes single natural product extracts for cancer-induced cachexia, not compounds derived from natural products and herbal medicine prescriptions. This article also discusses the effect of natural products on cachexia induced by anticancer drugs and the role of AMPK in cancer-induced cachexia. The article included the mice model used in each experiment to encourage researchers to utilize animal models for research on cancer-induced cachexia in the future. Full article
(This article belongs to the Special Issue AMP-Activated Protein Kinases in Health and Disease)
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