UV-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. 4. Calcium is involved in the cytotoxicity of UV-treated LDL on lymphoid cell lines

doi:10.1016/0005-2760(92)90113-A

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism

Volume 1123, Issue 2, 24 January 1992, Pages 207-215

Biochimica et Biophy...

https://doi.org/10.1016/0005-2760(92)90113-A Get rights and content

Abstract

In lymphoid cells pulsed with ‘cytotoxic’ concentrations of UV-treated LDL, the study of the variations of free cytosolic calcium concentration, of the influence of extracellular calcium and of the protective effect of calcium chelators suggests that both intra- and extracellular calcium could play a major role in the genesis of cell injury leading to cell death. (1) A dramatic sustained rise of cytosolic free calcium (the level of free cytosolic calcium was higher than 500 nmol /1 for 6 h or more) occurred several hours after the beginning of the pulse with UV-treated LDL (lag period between 6 and 12 h). (2) The rise of the free cytosolic calcium and the ‘cytotoxicity’ induced by UV-treated LDL were largely dependent on the concentration of extracellular calcium which has an effect on the uptake of UV-treated LDL and on the expression of the ‘cytotoxicity’ at the cellular level. (3) The study of the sequence of intracellular events showed that the cellular oxidative stress generated by oxidized LDL was followed by the rise of free cytosolic calcium and later by the rise of ‘cytotoxicity’ indexes. (4) The intracellular calcium chelators, BAPTA/AM and EGTA/AM, were able to partially protect lymphoid cells against the ‘cytotoxicity’ of oxidized LDL. The supposed mechanisms of the free cytosolic calcium rise and the respective role of calcium or/and other factors (for instance direct lesions of the plasma membrane by the oxidative stress due to oxidized LDL) in the genesis of cellular lesions leading to cell death are discussed.

References (48)

G. Jürgens et al.
Chem. Phys. Lipids
(1987)
M.E. Haberland et al.
Am. Heart
(1987)
U.P. Steinbrecher et al.
Free Rad. Biol. Med.
(1990)
J. Schuh et al.
Biochem. Biophys. Res. Commun.
(1978)
J.L. Hessler et al.
Atherosclerosis
(1979)
N. Dousset et al.
Biochim. Biophys. Acta
(1990)
A. Negre-Salvayre et al.
Biochim. Biophys. Acta
(1990)
H. Thor et al.
J. Biol. Chem.
(1982)
A.R. Boobis et al.
Trends Pharmacol. Sci.
(1989)
S. Orrenius et al.
Trends Pharmacol. Sci.
(1989)

R. Salvayre et al.

Biochim. Biophys. Acta

(1981)

D.P. Via et al.

Methods Enzymol.

(1986)

K. Mc Ginnes et al.

J. Immunol. Methods

(1986)

P. Arslan et al.

J. Biol. Chem.

(1985)

K. Yagi

Chem. Phys. Lipids

(1987)

O.H. Lowry et al.

J. Biol. Chem.

(1951)

J.L. Goldstein et al.

J. Biol. Chem.

(1974)

M. Kuzuya et al.

Biochim. Biophys. Acta

(1991)

P. Nicotera et al.

FEBS Lett.

(1986)

M. Kuzuya et al.

Biochem. Biophys. Res. Comm.

(1989)

A. Negre-Salvayre et al.

Biochim. Biophys. Acta

(1991)

S.C. Chow et al.

J. Biol. Chem.

(1990)

F.R. Ungemach

Chem. Phys. Lipids

(1987)

A.R. Boobis et al.

Biochem. Pharmacol.

(1990)

Cited by (32)

Dual signaling evoked by oxidized LDLs in vascular cells
2017, Free Radical Biology and Medicine
Citation Excerpt :
In contrast, oxLDLs elicit Mn-SOD degradation through JNK-dependent ubiquitination, thereby reducing mitochondrial antioxidant defenses and inducing endothelial cell apoptosis [158]. Moreover, lipid peroxides delivered by oxLDLs that are taken up by cells, induce sustained calcium signaling that triggers apoptosis [83,159]. Finally, low concentrations of oxLDLs and low levels of ROS induce vascular cell activation and pro-inflammatory responses of macrophages, while higher concentrations of oxLDLs elicit a toxic and pro-apoptotic effect [36,83,150].
The oxidative theory of atherosclerosis relies on the modification of low density lipoproteins (LDLs) in the vascular wall by reactive oxygen species. Modified LDLs, such as oxidized LDLs, are thought to participate in the formation of early atherosclerotic lesions (accumulation of foam cells and fatty streaks), whereas their role in advanced lesions and atherothrombotic events is more debated, because antioxidant supplementation failed to prevent coronary disease events and mortality in intervention randomized trials.
As oxidized LDLs and oxidized lipids are present in atherosclerotic lesions and are able to trigger cell signaling on cultured vascular cells and macrophages, it has been proposed that they could play a role in atherogenesis and atherosclerotic vascular remodeling.
Oxidized LDLs exhibit dual biological effects, which are dependent on extent of lipid peroxidation, nature of oxidized lipids (oxidized phospholipids, oxysterols, malondialdehyde, α,β-unsaturated hydroxyalkenals), concentration of oxidized LDLs and uptake by scavenger receptors (e.g. CD36, LOX-1, SRA) that signal through different transduction pathways. Moderate concentrations of mildly oxidized LDLs are proinflammatory and trigger cell migration and proliferation, whereas higher concentrations induce cell growth arrest and apoptosis. The balance between survival and apoptotic responses evoked by oxidized LDLs depends on cellular systems that regulate the cell fate, such as ceramide/sphingosine-1-phosphate rheostat, endoplasmic reticulum stress, autophagy and expression of pro/antiapoptotic proteins. In vivo, the intimal concentration of oxidized LDLs depends on the influx (hypercholesterolemia, endothelial permeability), residence time and lipid composition of LDLs, oxidative stress intensity, induction of defense mechanisms (antioxidant systems, heat shock proteins). As a consequence, the local cellular responses to oxidized LDLs may stimulate inflammatory or anti-inflammatory pathways, angiogenic or antiangiogenic responses, survival or apoptosis, thereby contributing to plaque growth, instability, complication (intraplaque hemorrhage, proteolysis, calcification, apoptosis) and rupture. Finally, these dual properties suggest that oxLDLs could be implicated at each step of atherosclerosis development, from early fatty streaks to advanced lesions, depending on the nature and concentration of their oxidized lipid content.
An exopolysaccharide from Trichoderma pseudokoningii and its apoptotic activity on human leukemia K562 cells
2012, Carbohydrate Polymers
Citation Excerpt :
These factors can activate caspase or caspase-independent effectors of apoptosis and produce the apoptotic phenotype (Dispersyn & Borgers, 2001; Galluzzi et al., 2008; Goldspink, Burniston, & Tan, 2003). Many studies have demonstrated that apoptosis was accompanied by an enhancement of intracellular Ca2+ (Kaneko & Tsukamoto, 1994; Nègre-Salvayre & Salvayre, 1992). It is interesting to know whether EPS induce K562 cells apoptosis with an increase of intracellular-free calcium concentration ([Ca2+]i).
In this study, a novel exopolysaccharide (EPS) was isolated from the fermentation broth of Trichoderma pseudokoningii and its anticancer activities on human leukemia K562 cells were studied. EPS could significantly inhibited K562 cells proliferation in a time- and concentration-dependent manner. Meanwhile, characteristic of apoptosis, including apoptotic morphological features and the apoptosis rate were obtained. Sequentially, the dissipation of mitochondrial membrane potential, increase production of Reactive oxygen species (ROS), enhancement of the concentration of intracellular, up-regulation of Bax and p53 mRNA, down-regulation of Bcl-2 mRNA were also detected. The results indicate that the EPS could induce of K562 cells apoptosis, primarily in involved the mitochondrial pathways. The present studies suggest that EPS could be a new potential adjuvant chemotherapeutic and chemo preventive agent against human leukemia.
Long term exposure to norharman exacerbates 6-hydroxydopamine-induced parkinsonism: Possible involvement of L-type Ca<sup>2+</sup> channels
2010, Behavioural Brain Research
β-Carbolines (BCs) are considered as endogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease (PD). However, several lines of evidences show that these compounds have neuroprotective effect. This study was designed to assess effect of long term exposure to norharman, a BC compound which in mammalian brain occurs at high levels in the substantia nigra, on the progress of parkinsonism induced by 6-hydroxydopamine (6-OHDA). Animals were daily treated by norharman at doses 100, 200 and 1000 μg/kg (i.p.) just before to four weeks after the intrastriatal injection of 6-OHDA. Statistical analysis of apomorphine-induced rotation tests demonstrates that treatment by norharman at doses 200 and 1000 μg/kg for four weeks exacerbates significantly behavioral symptoms of the parkinsonism. To explore mechanisms by which norharman affects nigral dopaminergic cells, we studied the role of L-type Ca²⁺ channels. For this purpose, animals were daily treated with either L-type Ca²⁺ channel blocker of nifedipine at doses 2 and 5 mg/kg (i.p.) or nifedipine together with norharman before to four weeks after the 6-OHDA injection. While treatment with nifedipine improved behavioral symptoms of the parkinsonism, treatment with both nifedipine and norharman had no affect on these symptoms. This data indicates that long term exposure to BCs promote nigral dopaminergic cell death possibly through L-type Ca²⁺ channels.
Induction of oxidative stress and apoptosis by pentachlorophenol in primary cultures of Carassius carassius hepatocytes
2009, Comparative Biochemistry and Physiology - C Toxicology and Pharmacology
Induction of calcium influx from extracellular fluid by beauvericin in human leukemia cells
2006, Biochemical and Biophysical Research Communications
Citation Excerpt :
Several recent studies have reported the involvement of Ca2+ in apoptotic processes [13,14]. The elevated [Ca2+]i causes proapoptotic protein expression [14]. The rise of [Ca2+]i has been demonstrated to cause mitochondrial inner transmembrane potential collapse and to induce the release of cytochrome c[15].
Beauvericin, a cyclic hexadepsipeptide, is a mycotoxin that can induce cell death in human lymphoblastic leukemia CCRF-CEM cells. Our previous data have shown that beauvericin induces cell death in CCRF-CEM cells in a dose- and time-dependent manner, and that this beauvericin-induced cell death can be prevented by administration of intracellular calcium chelator-BAPTA. Therefore, the intracellular Ca²⁺ concentration ([Ca²⁺]_i) may play an important role in beauvericin-induced cell death in CCRF-CEM cells. In this study, the effect of beauvericin on [Ca²⁺]_i and the possible mechanism responsible for the changes of [Ca²⁺]_i in CCRF-CEM cells were investigated. Beauvericin caused a rapid and sustained [Ca²⁺]_i rise in a dose-dependent manner. Excess extracellular Ca²⁺ facilitated beauvericin-induced [Ca²⁺]_i rise by adding 1 mM CaCl₂ in the bathing medium. On the other hand, beauvericin-induced [Ca²⁺]_i rise was prevented in Ca²⁺-free Tyrode’s solution by 200 μM EGTA. In addition, beauvericin-induced [Ca²⁺]_i rise was also attenuated by intracellular Ca²⁺ chelator-BAPTA/AM. It is worthy to note that neither the voltage-dependent Ca²⁺ channel blocker, nimodipine, nor depletion of intracellular Ca²⁺ with thapsigargin, an endoplasmic reticulum Ca²⁺ pump inhibitor, has any effect on beauvericin-induced [Ca²⁺]_i rise. The data from present study indicate that beauvericin acts as a potent Ca²⁺mobilizer by stimulating extracellular Ca²⁺ influx CCRF-CEM cells.
Intracellular-free calcium dynamics and F-actin alteration in the formation of macrophage foam cells
2005, Biochemical and Biophysical Research Communications
The formation of macrophage foam cells, which is the key event in atherosclerosis, occurs by the uptake of oxidized low-density lipoprotein (Ox-LDL) via the scavenger receptor (CD36) pathway. Ca²⁺ plays an important role in atherosclerosis. However, in the spatiotemporal view, the correlation between kinetic changes of intracellular-free calcium ([Ca²⁺]_i) and the cellular dysfunctions in the formation of macrophage foam cells has not yet been studied in detail. By the use of confocal laser scanning microscope and flow cytometer, we have detected Ca²⁺ dynamics, the assembly of F-actin, and the expression of CD36 under the exposure of U937-derived macrophages to Ox-LDL. The uptake of Ox-LDL significantly increased [Ca²⁺]_i in U937-derived macrophages in both acute and chronic treatments (P < 0.01). In particular, the increases of the induced [Ca²⁺]_i were different in the presence or absence of extracellular Ca²⁺ under acute exposure. A time-dependent rise in F-actin assembly and CD36 expression at 12 and 24 h was induced, respectively, by Ox-LDL. The spatiotemporal increases of [Ca²⁺]_i induced by Ox-LDL probably have the key effect on the early phrase in the formation of macrophage foam cells.

View all citing articles on Scopus

View full text

UV-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. 4. Calcium is involved in the cytotoxicity of UV-treated LDL on lymphoid cell lines

Abstract

Chem. Phys. Lipids

Am. Heart

Free Rad. Biol. Med.

Biochem. Biophys. Res. Commun.

Atherosclerosis

Biochim. Biophys. Acta

Biochim. Biophys. Acta

J. Biol. Chem.

Trends Pharmacol. Sci.

Trends Pharmacol. Sci.

Biochim. Biophys. Acta

Methods Enzymol.

J. Immunol. Methods

J. Biol. Chem.

Chem. Phys. Lipids

J. Biol. Chem.

J. Biol. Chem.

Biochim. Biophys. Acta

FEBS Lett.

Biochem. Biophys. Res. Comm.

Biochim. Biophys. Acta

J. Biol. Chem.

Chem. Phys. Lipids

Biochem. Pharmacol.