Ferroptosis-Induced Metabolic Shifts in Cardiac Cells: Exploring the Influence of Glutaminolysis | Chapter 4 | New Visions in Medicine and Medical Science Vol. 5

Aims: Ferroptosis, an iron-dependent non-apoptotic cell death mechanism, profoundly impacts cellular metabolism. Despite its significance, a comprehensive metabolomic analysis of ferroptotic cells remains elusive.

 

Study Design and Methodology:  In this study, we investigated the metabolome of H9c2 cardioblast cells using gas chromatography-mass spectrometry during ferroptosis induced by RSL3, an inhibitor of glutathione peroxidase 4. Notably, we explored the effects of ferroptosis inhibitors, including ferrostatin-1, and the mitochondrial-targeted ROS scavenger, XJB-5-131.

 

Place and Duration of Study: Department of Physiology and Department of Biochemistry, University of Puerto Rico School of Medicine, between October 2019 and September 2021.

 

Results: The results revealed a significant reduction of amino acids crucial for glutathione synthesis by more than two-fold upon RSL3 treatment. Conversely, saturated fatty acid levels were notably elevated in RSL3-exposed cells, with no discernible impact on unsaturated fatty acids. Moreover, RSL3 induced substantial alterations in mitochondrial tricarboxylic acid cycle intermediates; while isocitrate and 2-oxoglutarate levels increased, succinate levels decreased significantly in RSL3-treated cells. Importantly, ferrostatin-1 and XJB-5-131 effectively prevented RSL3-induced cell death and preserved the metabolic profile. Given the involvement of 2-oxoglutarate in ferroptosis regulation, particularly through glutamine metabolism, we further investigated the role of glutaminolysis in H9c2 cardi-oblasts ferroptosis. Silencing of glutaminase 1, encoding the K-type mitochondrial glutaminase (glutaminase C), conferred protection against ferroptosis at the early stage.

 

Conclusion: In conclusion, our study demonstrates the disruptive impact of RSL3-induced ferroptosis on the metabolome of H9c2 cardioblasts.

Author(s) Details:

Keishla M. Rodríguez-Graciani,
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Xavier R. Chapa-Dubocq,
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Esteban J. Ayala-Arroyo,
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Ivana Chaves-Negrón,
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Sehwan Jang,
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Nataliya Chorna,
Department of Biochemistry, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Taber S. Maskrey,
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.

Peter Wipf,
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.

Sabzali Javadov,
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.

Please see the link here: https://stm.bookpi.org/NVMMS-V5/article/view/14153

Ferroptosis and the Application of Traditional Chinese Medicine in Managing Type 2 Diabetes Mellitus | Chapter 10 | Novel Research Aspects in Medicine and Medical Science Vol. 7

 The research field of ferroptosis has happened enjoying exponential progress over the past few age, since the term was coined in 2012. This singular modality of container death, driven by iron-reliant phospholipid peroxidation, is regulated by diversified cellular metabolic events, containing redox homeostasis, iron management, mitochondrial activity, and metabolism of amino acids, lipids and sugars, apart from numerous signaling pathways having to do with disease. Intriguingly, medicine-resistant cancer containers, particularly those of the mesenchymal state and dependent on something metastasis, are exquisitely ready to ferroptosis. Ferroptosis, an emerging form of controlled programmed cell dying, has garnered meaningful attention in the past ten of something. It is characterized by the accumulation of lipid peroxides and after damage to cellular membranes, that is dependent on iron. Under iron-rich and ROS conditions, phospholipids holding polyunsaturated fatty acids in the container membranes are prone to peroxidation, resulting in the unending accumulation of lipid peroxidation commodity. These products eventually upset cell sheet integrity and induce container death. Ferroptosis has been involved in the pathogenesis of various ailments, including tumors and diabetes mellitus. Traditional Chinese medicine (TCM) has singular advantages in forbiding and treating type 2 diabetes mellitus (T2DM) due to allure anti-angering, antioxidant, immunomodulatory, and intestinal flora-managing functions. Recent studies have determined that TCM may apply therapeutic belongings on T2DM and its complications by modulating the ferroptosis-accompanying pathways. Therefore, a comprehensive and orderly understanding of the role of ferroptosis in the pathogenesis and TCM treatment of T2DM is of excellent significance for evolving therapeutic drugs for T2DM and enriching the range of effective T2DM situation with TCM. In this review, we review the concept, method, and regulatory pathways of ferroptosis and the ferroptosis mechanism of operation involved in the incident of T2DM. Also, we develop a search strategy, organize strict addition and exclusion criteria, and recap and analyze the use of the ferroptosis mechanism in TCM studies related to T2DM and allure complications. Finally, we explain the shortcomings of current studies and propose a future research focus.

Author(s) Details:

Dandan Xie,
College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, People’s Republic of China and Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Health Management Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China and Department of Clinical Nutrition, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, People’s Republic of China.

Kai Li,
College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, People’s Republic of China.

Ruxue Feng,
Department of Stomatology, Geriatric Hospital of Hainan, Haikou, Hainan, People’s Republic of China.

Man Xiao,
Department of Biochemistry and Molecular Biology, Hainan Medical University, Haikou, Hainan, People’s Republic of China.

Zhifeng Sheng,
Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Health Management Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China.

Yiqiang Xie,
College of Traditional Chinese Medicine, Hainan Medical University, Haikou, Hainan, People’s Republic of China.

Please see the link here: https://stm.bookpi.org/NRAMMS-V7/article/view/12174

Comparative Study of Common Antioxidants and Dithiooxamide in Lipid Autoxidation | Chapter 2 | Current Practice in Medical Science Vol. 4

The writers have studied antioxidants, oxidation, and anti-aging since the 1980s. They learned that since lipids are some of the most widely used basic materials in foods, cosmetics, and the human body, it would be wise to look at autoxidation in this context, whether to stop spoilage or slow ageing.

The researchers selected a few lipids for an autoxidation inquiry and compared them to common pro-oxidants and antioxidants, as well as a possible antioxidant candidate, along with an evaluation of their short-term toxicity. The lipids were heated up while being subjected to a number of pro-oxidants, common commercial antioxidants, the antioxidant candidate, and a control. After that, the authors performed a short-term toxicity assessment and an analysis of the lipids for oxidation by-products. Autoxidation is more likely to occur in lipids that have been exposed to heavy metals like iron, copper, or other heavy metals or that have been polluted with them. In contrast to other metals, aluminium does not appear to hasten the autoxidation of lipids. The antioxidant candidate dithiooxamide appears to be a capable antioxidant with no short-term toxicity in a small sample study, which was far below the LDLo and LD50 conducted on rats and mice using dithioxamide in other later published research. This is in contrast to antioxidants like vitamin E, BHA, BHT, and PG. The results indicate that iron, copper, and other heavy metals should be avoided when using lipids, and that the antioxidant candidate dithiooxamide may be useful for exterior lipid applications when used sparingly.

Author(s) Details:

Seamus C. C. Phan,

10 Anson Road, #03-19, International Plaza, Singapore 079903, Singapore.

Please see the link here: https://stm.bookpi.org/CPMS-V4/article/view/7357