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10th International Congress "Cell Volume Regulation: Novel Therapeutic Targets and Pharmacological Approaches"
DIFFERENTIAL EFFECTS OF OXLDL COMPONENTS ON ENDOTHELIAL BIOMECHANICAL PROPERTIES
Shentu, T.-P., Singh, D., Subbaiah, P., Cho, M., and Levitan, I.
Department of Medicine, University of Illinois at Chicago, USA
Endothelial biomechanical properties have been suggested to play important roles in multiple endothelial functions. Our earlier studies have shown that endothelial stiffness is significantly increased by oxidized modifications of low-density lipoproteins (oxLDL). The goal of the current study was to identify the bioactive oxLDL components that are responsible for this effect. To address this goal, we systematically tested all the lipid fractions and the major bioactive lipid components of oxLDL for their effects on endothelial stiffness. We show here that the two fractions that contribute to the increase in endothelial stiffness are oxidized phospholipids (oxPC) and oxysterols. Furthermore, we show that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine
(oxPAPC), a major oxPC component, and 7-ketocholesterol and 7a-hydroxycholesterol, the two major oxysterol components of oxLDL, play the key roles in endothelial stiffening. In addition, 27-hydroxycholesterol, a minor component of oxLDL that is abundant in atherosclerotic lesions also induces an increase in endothelial stiffness. We also find that oxPAPC- and oxysterol-induced endothelial stiffening is fully reversible by cholesterol supplement suggesting that this effect should be attributed to changes in the lipid composition of the membrane. Indeed, we show that significant amounts of oxidized PC products and oxysterols, specifically, 7-ketocholesterol accumulate in the membranes of endo-thelial cells exposed to oxLDL.
PARTICIPATION OF P38 MAPK IN APOPTOTIC VOLUME DECREASE IN JURKAT CELLS TREATED BY GAS TRANSMITTERS
Starikova, Ye.G., Tashireva, L.A., Novitsky, V.V., and Ryazantseva, N.V.
Siberian State Medical University, Tomsk, Russian Federation
It has been shown that the volume decrease is an early essential component of apoptotic cell death. Activation of stress-responsive MAPKs (JNK and p38) was reported to mediate activation of volume-sensitive outwardly rectifying anion channels in several cell types [1-4]. Participation of gaseous transmitters (nitric oxide, hydrogen sulfide, carbon monoxide) in apoptosis regulation is one of the intriguing field of up-to-day science.
Contribution of p38 MAPK in apoptosis development will be investigated in this work. p38 MAPK participation in apoptosis regulation in cells treated by gas transmitters could be the evidence of this kinase role in functioning of volume-sensitive outwardly rectifying anion channels in above mentioned conditions.
We have shown that p38 MAPK acted proapoptotically in the cases of intracellular increase of nitric oxide and hydrogen sulfide and antiapoptotically in carbon monoxide-treated cells. As the role of p38 MAPK could vary from proapoptotic to antiapoptotic in the case of different gas transmitters action this molecule could have activating as
well as inhibiting influence on volume-sensitive outwardly rectifying anion channels in the case of nitric oxide, hydrogen sulfide and carbon monoxide intracellular level increase.
References
1. Redman, P.T., He, K., Hartnett, K.A., Jefferson, B.S., Hu, L., Rosenberg, P.A., Levitan, E.S., Aizenman, E. Apoptotic surge of potassium currents is mediated by p38 phosphorylation of Kv2.1. Proc. Natl. Acad. Sci. USA., 2007, 104, pp. 3568-3573.
2. Bossy-Wetzel, E., Talantova, M.V., Lee, W.D., Schölz-ke, M.N., Harrop, A., Mathews, E., Götz, T., Han, J., Ellisman, M.H., Perkins, G.A., et al. Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mi-tochondrial dysfunction and p38-activated K+ channels. Neuron, 2004, 41, pp. 351-365.
3. Gao, J., Wu, D., Guo, T.B., Ruan, Q., Li, T., Lu, Z., Xu, M., Dai, W., Lu, L. K+ channel activity and redox status are differentially required for JNK activation by UV and reactive oxygen species. Exp. Cell Res., 2004, 297, pp. 461-471.
4. Heimlich, G., Cidlowski, J.A. Selective role of intracellular chloride in the regulation of the intrinsic but not extrinsic pathway of apoptosis in Jurkat T-cells. J. Biol. Chem., 2006, 281, pp. 2232-2241.
Бюллетень сибирской медицины, 2013, том 12, № 4, с. 24-68
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