Apoptosis vs. oncosis: role of cell volume and intracellular monovalent cations

Advances in Experimental Medicine and Biology
Sergei N Orlov, Pavel Hamet

Abstract

Several research teams have proposed that shrinkage and swelling in cells undergoing apoptosis and oncosis are not only the earliest morphological markers of the two modes of cell death but are also obligatory steps in the development of the death machinery. We examined this hypothesis as well as the role of monovalent cations as major intracellular osmolytes using vascular smooth muscle cells (VSMC) from the rat aorta and C7-MDCK cells derived from the Madin-Darby canine kidney. 48-hr inhibition of the Na(+)-K+ pump with ouabain did not affect VSMC survival and delayed serum deprivation-induced apoptosis at a step upstream of caspase-3 via elevation of the [Na+]i/[K+]i ratio and the expression of Na+ i-sensitive antiapoptotic genes including mortalin. Transient and modest (15-20%) shrinkage observed in serum-deprived VSMC did not contribute to triggering of the apoptotic machinery. In contrast to VSMC, ouabain led to oncosis of C7-MDCK cells, indicated by swelling and resistance to the pan-caspase inhibitor z-VAD.fmk. In these cells, the death signal was mediated by interaction of ouabain with the Na(+)-K(+)-ATPase alpha-subunit but was independent of the inhibition of Na(+)-K+ pump-mediated ion fluxes and elevation of the [Na...Continue Reading

Citations

Apr 26, 2013·American Journal of Physiology. Cell Physiology·Sergei N OrlovRyszard Grygorczyk
Jun 23, 2020·Biochemistry. Biokhimii︠a︡·E A KlimanovaS N Orlov
Oct 16, 2012·Pflügers Archiv : European journal of physiology·J Marc SimardVolodymyr Gerzanich
Aug 16, 2006·The Journal of Membrane Biology·S N Orlov, P Hamet
Apr 20, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sergei N OrlovOlga D Lopina
Dec 18, 2013·The Journal of Physiology·Florian Lang, Else K Hoffmann
Oct 31, 2014·The Journal of Biological Chemistry·Christopher Del NagroThomas O'Brien
Jan 22, 2020·Genes & Diseases·Sergei N OrlovElizaveta A Klimanova
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Markus RitterHubert H Kerschbaum
Jul 22, 2006·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Olga AkimovaSergei N Orlov
Sep 28, 2021·Frontiers in Cell and Developmental Biology·Markus RitterYasunobu Okada

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