Iron supplementation evaluation on cardiomyocyte functions in response to conditioned medium mimicking cancer cachexia

• Grant number: 22/07126-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): November 01, 2022
• Effective date (End): April 30, 2023
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Maria Cristina Cintra Gomes Marcondes
• Grantee: Maiara Caroline Colombera
• Supervisor: Paolo Ettore Porporato
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: Università degli Studi di Torino (UNITO), Italy
• Associated to the scholarship: 20/13222-5 - Evaluation of leucine supplementation on the tumor factors effects in H9c2 cardiac cells, BP.MS

Abstract

Cancer cachexia is a complex, systemic, multifactorial syndrome that causes several metabolic alterations, affecting multiple organs, including the heart. Cardiac failures in patients with cancer cachexia have been widely reported, representing a severe problem limiting patient survival, but often underestimated and insufficiently studied. Cancer and heart diseases have been associated with iron deficiency, which can leads to mitochondrial dysfunction and alterations in cardiomyocyte microfilaments. In view of the recently established role of iron supplementation as a potential therapeutic option for cancer-cachexia, this project aims to investigate the effects of iron in cardiac cells exposed to a conditioned medium (CM) from cancer cells and treated with ferric citrate (Fe). For this purpose, we will determine cell diameter, iron uptake, mitochondrial metabolism, mitochondrial DNA (mtDNA), P-Thr172- AMPK, Total-AMPK, Ferritin, IRP2, Transferrin Receptor, NCOA4, total OXPHOS, and Ferroportin proteins, and myosin heavy chain in cardiac cells (H9c2 or cardiac primary culture cell) exposed to CM from C26 cells colon cancer. Besides, to verify if iron availability is sufficient for cardiomyocyte alterations, cells will be treated with different iron chelators, to verify if the protective effects of iron are mediated by mitochondrial function, cells will be exposed to different atrophy inductors. To analyse the transferrin receptor (TFR1), the green fluorescent protein (GFP), and a cytoplasmic protein that mediates autophagic degradation of ferritin (NCOA4) role in cardiac muscle fibre homeostasis, will be realised transfection with esiTFR1, esiNCOA4 and esiGFP.