Boczek 2014 Biomed Res Int

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Boczek T, Lisek M, Ferenc B, Kowalski A, Wiktorska M, Zylinska L (2014) Silencing of plasma membrane Ca2+-ATPase isoforms 2 and 3 impairs energy metabolism in differentiating PC12 cells. Biomed Res Int 2014:735106.

» PMID:25276815

Boczek T, Lisek M, Ferenc B, Kowalski A, Wiktorska M, Zylinska L (2014) Biomed Res Int

Abstract: A close link between Ca2+, ATP level, and neurogenesis is apparent; however, the molecular mechanisms of this relationship have not been completely elucidated. Transient elevations of cytosolic Ca2+ may boost ATP synthesis, but ATP is also consumed by ion pumps to maintain a low Ca2+ in cytosol. In differentiation process plasma membrane Ca2+ ATPase (PMCA) is considered as one of the major players for Ca2+ homeostasis. From four PMCA isoforms, the fastest PMCA2 and PMCA3 are expressed predominantly in excitable cells.

In the present study we assessed whether PMCA isoform composition may affect energy balance in differentiating PC12 cells. We found that PMCA2-downregulated cells showed higher basal O2 consumption, lower NAD(P)H level, and increased activity of ETC. These changes associated with higher [Ca2+]c resulted in elevated ATP level. Since PMCA2-reduced cells demonstrated greatest sensitivity to ETC inhibition, we suppose that the main source of energy for PMCA isoforms 1, 3, and 4 was oxidative phosphorylation. Contrary, cells with unchanged PMCA2 expression exhibited prevalence of glycolysis in ATP generation. Our results with PMCA2- or PMCA3-downregulated lines provide an evidence of a novel role of PMCA isoforms in regulation of bioenergetic pathways, and mitochondrial activity and maintenance of ATP level during PC12 cells differentiation.

Keywords: PC12 rat pheochromocytoma cells


Labels: MiParea: Respiration, Developmental biology 


Organism: Rat  Tissue;cell: Nervous system, Other cell lines 

Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase  Regulation: ATP production, Calcium  Coupling state: LEAK, ROUTINE, ET 

HRR: Oxygraph-2k 


Correction

An Oroboros Oxygraph-2k was used in this publication, whereas the Anton Paar/Oroboros Oxygraph was the first-generation instrument for high-resolution respirometry, which was replaced by the Oxygraph-2k in 2002.