MITOCHONDRIAL RESPIRATORY PARAMETERS AND BIOGENESIS REGULATORY FACTORS ARE INCREASED BY ANGIOTENSIN II IN H295R HUMAN ADRENOCORTICAL CELLS

BELLUNO MATÍAS; HELFENBERGER KATIA E.; MARTÍNEZ BALCAZAR ARIANA ; BOZZANO ALEJANDRA; CASTILLO, ANA F.; BENZO YANINA; PODEROSO CECILIA

Mar del Plata

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2022

SAIC

Mitochondrial homeostasis is preserved by the fine coordination between the generation of new mitochondria by mitochondrial biogenesis; and the removal of damaged mitochondria. Biogenesis increases oxidative phosphorylation capacity, diminishes pathologic oxidative stress and repair mitochondrial-associated dysfunctions. This process is driven by transcription factors such as PCG-1, TFAM, NRF1 and usually is accompanied by an increase in mitochondrial DNA (mtDNA). Mitochondrial normal function is essential for hormones signal transduction pathway, such as angiotensin II (Ang II). We have previously reported that Ang II favors mitochondrial fusion in H295R human adrenocortical cells. The effect of Ang II on mitochondrial regulators genes and metabolic parameters is not known up to date. The aim of this work is to determine the effect of Ang II on several transcription factors involved in the regulation of mitochondrial parameters in H295R cells. We observed that 100 nM Ang II promoted a significant increase in NRF1 mRNA levels in a time-dependent manner, as assessed by qPCR (p0.001). Furthermore, after Ang II stimulation, a significant increase on TFAM protein levels was detected by western blot (p0.05). In agreement, mitochondrial mass increased in response to Ang II treatment, determined by the relationship between nuclear DNA and mtDNA by qPCR. mRNA expression of NRF2 and UCP2, genes involved in mitochondrial function, is regulated by Ang II in a biphasic manner. Then, we analyzed mitochondrial bioenergetics in Ang II-stimulated and control cells by using the SeaHorse XF Cell Mito Stress Test and observed that mitochondrial basal and maximal respiration and ATP production are significantly increased by this hormone (p