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First published online January 17, 2007
Journal of Experimental Biology 210, 438-446 (2007)
Published by The Company of Biologists 2007
doi: 10.1242/jeb.02680
Cu2+ and acute thermal stress induce protective events via the p38-MAPK signalling pathway in the perfused Rana ridibunda heart
Department of Animal and Human Physiology, School of Biology, Faculty of Sciences, University of Athens, Panepistimioupolis, Athens 157 84, Greece
* Author for correspondence (e-mail: ibeis{at}biol.uoa.gr)
Accepted 5 December 2006
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Summary |
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Key words: oxidative stress, thermal stress, copper, antioxidants, p38-MAPK, Hsp27, amphibian heart, Rana ridibunda, signal transduction
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Introduction |
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TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
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). On the other hand, ectothermic vertebrates, like
amphibians, face a wide range of seasonal variations in their natural
environment (Hoffman and Katz,
1997; Hutchison and Dupr,
1992), such as low oxygen pressure or temperature imbalances
(Hermes-Lima and Storey, 1996;
Hermes-Lima and Storey, 1998;
Greenway and Storey, 2000),
which are related to increased production of reactive oxygen species (ROS),
while their skin is a site for gas exchange and high permeability to water
(Katz et al., 1986). As a
result, these organisms have developed effective antioxidant defences so as to
adapt to the adverse environmental conditions
(Hermes-Lima and Storey, 1996;
Hermes-Lima and Storey,
1998).
Copper, a heavy transition metal, can exist in both an oxidized, cupric
(Cu2+), or reduced, cuprous (Cu+) state
(Linder and Hazegh-Azam, 1996)
and is able to move across cell membranes or through ion channels
(Handy et al., 2002) into the
cells. As a redox-active metal, copper plays important catalytic roles as a
cofactor in many enzymes such as copper-zinc superoxide dismutase and
cytochrome oxidase, which renders it an essential trace element for all
aerobic organisms (Solomon and Lowery,
1993; Gaetke and Chow,
2003). At elevated cellular copper levels, rapid generation of ROS
is induced via a Haber-Weiss or Fenton-like reaction
(Gutteridge, 1985;
Shi and Dalal, 1992;
Gaetke and Chow, 2003).
Interestingly, copper catalyzes the formation of hydroxyl radicals, which lead
to oxidative damage of lipids, proteins and nucleic acids
(Gaetke and Chow, 2003). In
addition, this metal can be toxic by direct binding to protein sulfhydryl
groups, which results in enzyme inactivation or altered protein conformation
(Jeon et al., 2000). Recent
studies have demonstrated that copper accumulates in the tissues of the
amphibian Rana ridibunda
(Papadimitriou and Loumbourdis,
2003), the experimental model used in the present study.
Another well-established environmental parameter with profound effects on
cellular biochemistry, morphology and function, is temperature. In fact, this
variable determines the activity of cellular multi-enzyme systems, the
kinetics and flux throughout biochemical pathways and, in particular, the
metabolic rates. Amphibians normally experience rapid and intense variations
in body temperature (Tb) and appear to tolerate such
changes with minimal metabolic cost. They utilise physiological mechanisms
such as controlled evaporative water loss or peripheral
vasodilation/constriction to affect small changes in Tb
(Lillywhite, 1971;
Shoemaker et al., 1989). In
case of extreme temperature changes, thermal stress results in elevated
generation of ROS as well as alterations in intracellular antioxidant capacity
(Bagnyukova et al., 2003;
Gius et al., 2004).
Interestingly, mitochondria undergo a temperature-dependent uncoupling of the
respiratory chain leading to generation of ROS, thereby increasing the risk of
oxidative cell damage (Schiaffonati et
al., 1990; Salo et al.,
1991).
The disturbances in the physiological context of a cell can trigger the
activation of diverse intracellular signal transduction pathways, which
determine the cell fate by regulating gene expression and the activation of
protective or pro-apoptotic proteins. Among these signalling pathways the
mitogen-activated protein kinase (MAPK) ones are included
(Kyriakis and Avruch, 2001)
and various reports have documented their involvement in thermal- and
redox-stressed cells and tissues, including cardiac myocytes and intact
myocardium (Turner et al.,
1998; Bogoyevitch,
2000; Gaitanaki et al.,
2003; Gaitanaki et al.,
2006; Vassilopoulos et al.,
2005; Aggeli et al.,
2002; Aggeli et al.,
2006). However, the factors that modulate these pathways have not
been clarified in any system studied to date.
In the present study, we describe the effect of copper on the phosphorylation of p38-MAPK in the amphibian heart. The simultaneous impact of copper and acute thermal stress, as well as the effect of various antioxidants on the p38-MAPK signal transduction pathway, are also determined.
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Materials and methods |
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Animals
Frogs (Rana ridibunda Pallas) weighing 120–150 g were caught
in the vicinity of Thessaloniki, Greece, and supplied by a local dealer. They
were kept in containers in fresh water and received humane care in accordance
to the Guidelines for the Care and Use of Laboratory Animals published by the
Greek Government (160/1991) based on EC regulations (86/609). They were used a
week after arrival.
Heart perfusions
Animals were anesthetized by immersion in 0.05% (w/v) MS222 and their
hearts were excised and preserved in an ice-cold solution similar to the one
used for the perfusion. Then, the hearts were mounted onto the aortic cannula
of a conventional Langendorff perfusion system. Perfusions were performed in a
non-recirculating Langendorff mode at a pressure of 4.5 kPa (31.5 mmHg). The
standard perfusion buffer used was the Krebs bicarbonate-buffered saline (23.8
mmol l–1 NaHCO3, 103 mmol l–1
NaCl, 1.8 mmol l–1 CaCl2, 2.5 mmol
l–1 KCl, 1.8 mmol l–1 MgCl2, 0.6
mmol l–1 NaH2PO4, pH 7.4 at 25°C)
supplemented with 10 mmol l–1 glucose and equilibrated with
95% O2/5% CO2. The temperature of the hearts and
perfusates was maintained at 25°C using a water-jacketed apparatus. All
hearts were equilibrated for 30 min under these conditions. All ingredients
used were directly diluted in the Krebs bicarbonate-buffered saline.
Control hearts (Con) were perfused for 30 min at 25°C with the bicarbonate-buffered saline described above. As positive controls, we used hearts perfused with 50 µmol l–1 H2O2 for 2 min, after a 30 min equilibration period with the normal Krebs buffer. To examine the effect of the trace metal Cu2+, hearts were equilibrated as previously and perfused for 15 min with increasing concentrations of CuCl2 (50–500 µmol l–1) diluted in the bicarbonate-buffered saline. Perfusions were also conducted in the presence of the specific p38-MAPK inhibitor SB203580 (1 µmol l–1), during both the equilibration period and the perfusion with 500 µmol l–1 CuCl2 for 15 min. In another series of experiments, hearts were re-perfused with normal bicarbonate-buffered saline for time periods varying from 2 to 60 min, after the p38-MAPK maximal activation was reached. Moreover, the potent antioxidant activity of L-ascorbic acid (ASC) was investigated by perfusing hearts with 100 µmol l–1 ASC during both the equilibration period and the following perfusion with 500 µmol l–1 CuCl2 for 15 min. Hearts were also perfused for 45 min with normal perfusion buffer containing ASC (100 µmol l–1). In other experiments, after the 30 min equilibration period, temperature was increased up to 42°C, by using a second water-jacketed apparatus, and perfusions were conducted for 15 min under these conditions in the absence or presence of 500 µmol l–1 CuCl2. In the last series of experiments, hearts, after being equilibrated with normal bicarbonate-buffered saline, were perfused for 15 min with 500 µmol l–1 CuCl2 in the presence of catalase (CAT; 150 U ml–1), SOD (30 U ml–1) or CAT+SOD, at either 25°C or 42°C. All experimental conditions are illustrated in Fig. 1.
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At the end of the perfusions, atria were removed and the ventricles frozen by immersion in liquid N2, then pulverized under liquid N2. Tissue powders were stored at –80°C.
Tissue extractions
Heart powders were homogenized with 3 ml g–1 of buffer [10
mmol l–1 Hepes, pH 7.9, 10 mmol l–1 EGTA,
0.1 mmol l–1 EDTA, 10 mmol l–1 NaF, 1 mmol
l–1 Na3VO4, 1.5 mmol
l–1 MgCl2, 20 mmol l–1
ß-glycerophosphate, 1 mmol l–1 dithiothreitol (DTT), 2
µg ml–1 leupeptin, 0.5 mmol l–1 phenyl
methyl sulphonyl fluoride (PMSF), 4 µg ml–1 aprotinine]
and extracted on ice for 30 min. The samples were centrifuged (10000
g, 10 min, 4°C) and the supernatants boiled with 0.33 vol.
SDS-PAGE sample buffer [0.33 mol l–1 Tris-HCl, pH 6.8, 10%
(w/v) SDS, 13% (v/v) glycerol, 20% (v/v) 2-mercaptoethanol, 0.2% (w/v)
Bromophenol Blue]. Protein concentrations were determined using the Bio-Rad
Bradford assay.
SDS-PAGE and immunoblot analysis
Proteins were separated by SDS-PAGE on 10% (w/v) acrylamide, 0.275% (w/v)
bis-acrylamide or 15% (w/v) acrylamide, 0.413% (w/v) bis-acrylamide slab gels
and transferred electrophoretically onto nitrocellulose membranes (0.45
µm). Membranes were then incubated in TBS-T [20 mmol l–1
Tris-HCl, pH 7.5, 137 mmol l–1 NaCl, 0.05% (v/v) Tween 20]
containing 1% (w/v) bovine serum albumin (BSA) for 30 min at room temperature.
Subsequently, the membranes were incubated with the appropriate primary
antibody according to the manufacturer's instructions. After washing in TBS-T
(4x5 min) the blots were incubated with peroxidase-conjugated
anti-rabbit IgG antibodies [1:5000 dilution in TBS-T containing 1% (w/v) BSA
for 1 h at room temperature]. The blots were washed again in TBS-T (4x5
min) and the bands were detected using the enhanced chemiluminescence (ECL)
reaction with exposure to X-OMAT AR film. Blots were quantified by laser
scanning densitometry.
Statistical evaluations
All data are presented as means ± s.e.m. Comparisons between control
and treatments were performed using the unpaired Student's t-test. A
value of P<0.05 was considered to be statistically significant.
All values were normalized against total protein levels. Kinase and Hsp27
phosphorylation in `control' hearts were set at 1, and the stimulated kinase
and Hsp27 phosphorylation in treated hearts were expressed as `-fold'
activation over control hearts.
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). The
results of this study revealed that CuCl2 induced the activation of
p38-MAPK in a dose-dependent manner. As can be seen in
Fig. 2Ai,B, 50 µmol
l–1 of this trace metal, in the form of CuCl2,
induced a strong p38-MAPK phosphorylation (4.78±1.04-fold relative to
control values), whereas 500 µmol l–1 CuCl2
induced maximal activation of the kinase (8.73±1.43-fold relative to
control values). As a positive control, extract from hearts perfused with 50
µmol l–1 H2O2 for 2 min was used
(Fig. 2Ai). Equal protein
loading was confirmed by detecting actin protein levels of identical samples
(Fig. 2Aii).
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;
Rouse et al., 1994;
Gaitanaki et al., 2003). The
phosphorylation state of Hsp27 was assessed by immunoblot analysis using a
rabbit polyclonal antibody that detects the phosphorylated Hsp27 at Ser82. As
can be seen in Fig. 2C,D the
phosphorylation of Hsp27 follows a similar dose-dependent pattern to the one
observed for p38-MAPK. What is more, both the p38-MAPK and Hsp27
phosphorylations induced by 500 µmol l–1 CuCl2
were abolished by 1 µmol l–1 of the selective p38-MAPK
inhibitor, SB203580 (Fig. 3),
confirming that Hsp27 is indeed a downstream member of the p38-MAPK
pathway.
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In parallel, the effect of these stressful conditions on the Hsp27 phosphorylation was tested. The results of these experiments revealed that CuCl2 or hyperthermia (42°C) alone induced a significant increase in the Hsp27 phosphorylation (CuCl2: 6.24±0.59-fold relative to control values; hyperthermia: 7.86±0.40-fold relative to control values), whereas the combined effect of CuCl2 and hyperthermia did not result in an additive Hsp27 phosphorylation (6.69±0.58-fold relative to control values) (Fig. 5C,D).
In order to determine whether CuCl2-induced p38-MAPK phosphorylation was due to ROS produced in our experimental model by this trace metal, we performed perfusions in the presence of different antioxidants. First, we perfused amphibian hearts with the potent antioxidant L-ascorbic acid (100 µmol l–1) in either the absence or presence of 500 µmol l–1 CuCl2. The results of this study revealed that CuCl2-induced activation of p38-MAPK (8.73±1.43-fold relative to control values) was not changed by L-ascorbic acid (11.24±0.57-fold relative to control values) (Fig. 6Atop,B). Heart perfusions with L-ascorbic acid alone showed that this agent had no effect on the activation of p38-MAPK. Blots assayed with an anti-actin antibody were used as a control for equivalent protein loading (Fig. 6Abottom).
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Finally, we examined whether perfusions for 15 min with 500 µmol l–1 CuCl2, in the absence or presence of the antioxidant enzymes CAT and SOD, either at normal temperature or under hyperthermia, induced the activation of the pro-apoptotic marker caspase-3. For this reason we performed immunoblotting using a specific antibody that recognizes both the inactive pro-caspase and the active fragmented form of the protease. Our results revealed that under all conditions tested, only the full-length pro-caspase was detected, suggesting therefore, that caspase-3 was not activated (Fig. 8).
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Discussion |
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TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
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; Aggeli et al.,
2001b; Aggeli et al.,
2002; Gaitanaki et al.,
2003; Gaitanaki et al.,
2006). In particular, in the latter case, the stress was exerted
by using different oxidative factors such as H2O2 and
the enzymatic system of xanthine/xanthine oxidase
(Gaitanaki et al., 2003;
Gaitanaki et al., 2006;
Vassilopoulos et al.,
2005).
In the present study, we sought to investigate whether p38-MAPK signalling
pathway in the amphibian heart is also activated by copper, in the form of
CuCl2, a trace metal known to be associated with the induction of
oxidative stress (Gutteridge,
1985; Shi and Dalal,
1992; Gaetke and Chow,
2003). Our results revealed that CuCl2 activates
p38-MAPK in a dose-dependent manner (Fig.
2), with maximum activation attained by 500 µmol
l–1 of this agent. These results are in agreement with
several previous studies showing that CuCl2 leads to significant
p38-MAPK phosphorylation in diverse kinds of tissues and cell types, including
the mantle and gill tissues of the mussel Mytilus galloprovincialis
(Kefaloyianni et al., 2005),
trout hepatoma cells (Burlando et al.,
2003), human bronchial epithelial cells
(Samet et al., 1998) and human
pulmonary artery endothelial cells (Li et
al., 2005). The concentrations of the agent and the time-points
where maximum p38-MAPK activation was observed varied among individual
studies, reflecting the differences in the experimental models.
The effect of CuCl2 on kinase phosphorylation levels was doubled after a 2 min reperfusion period with normal bicarbonate-buffered saline and was sustained even after 60 min of CuCl2 withdrawal (Fig. 4). This considerable effect of reperfusion on p38-MAPK activation may be due to the fact that Cu2+ could not be removed from the heart tissue and this might enhance the kinase activation.
Recent studies have also revealed that hyperthermia is likely to lead to
the activation of multiple protein kinases, including p38-MAPK
(Woessmann et al., 1999;
Aggeli et al., 2002), which may
then regulate the stress response either by facilitating the repair of damaged
proteins and other cellular components or by inducing apoptosis
(Woessmann et al., 1999). In
their natural environment, amphibians could be simultaneously affected by both
thermal stress, due to elevated ambient temperatures, and increased levels of
copper, because of water pollution. Therefore, we examined the combined impact
of CuCl2 and hyperthermia (42°C) in the amphibian heart. Our
results confirmed that thermal stress activates p38-MAPK in the frog heart and
that its combination with CuCl2 has an additive effect on the
kinase phosphorylation (Fig.
5), a result that agrees with our previous studies performed in
the mantle tissue of Mytilus galloprovincialis
(Kefaloyianni et al.,
2005).
In order to determine whether the p38-MAPK activation by CuCl2
at normal temperature (25°C) or at 42°C was due to the production of
oxidative factors, we conducted perfusions in the abovementioned conditions in
the presence of SOD, catalase or both of them. At 25°C, neither SOD nor
catalase had any significant effect on the CuCl2-induced p38-MAPK
activation, suggesting that the ROS scavenged by these enzymes are not
implicated in the kinase activation at this temperature. In the case of the
combined action of hyperthermia and CuCl2, only catalase attenuated
the p38-MAPK activation down to the level of the CuCl2-stimulated
p38-MAPK activation at 25°C and this result is indicative of the
H2O2 production during hyperthermia
(Fig. 7). This also agrees with
a previous study, which reports the induction of oxidative stress in Rana
ridibunda after great change in the animal's body temperature
(Bagnyukova et al., 2003). By
contrast, when catalase was combined with SOD in the aforementioned
conditions, the activation of p38-MAPK was enhanced in comparison to the one
obtained when hearts were perfused with CuCl2 at 42°C
(Fig. 7). This last result
could be attributed to the fact that, in the presence of
H2O2, Cu and Cu/Zn SOD can induce the formation of the
carbonate anion radical from bicarbonate, the standard buffer used in this
study (Liochev and Fridovich,
2002; Liochev and Fridovich,
2006). This ROS could also participate in the activation of the
p38-MAPK signalling pathway in the amphibian heart.
Another potent antioxidant tested was L-ascorbic acid, which other studies
have shown that naturally exists in the amphibians
(Singh and Sinha, 1990).
Previously, we had demonstrated that this factor attenuated the
H2O2-induced p38-MAPK activation in the perfused
amphibian heart, but it had no impact on the kinase phosphorylation levels
induced by xanthine/xanthine oxidase system
(Gaitanaki et al., 2006). In
the present study, L-ascorbic acid also did not abolish the
CuCl2-induced p38-MAPK phosphorylation at 25°C
(Fig. 6), indicating that, in
the case of CuCl2, this agent does not function as an
antioxidant.
Since at normal temperature (25°C), p38-MAPK activation by copper is
not mediated by oxidative factors, it could be suggested that this stimulation
is possibly mediated by conformational changes in membrane proteins that
participate in signal transduction pathways
(Wu et al., 1999;
Letelier et al., 2005). In
addition, copper has been proposed to inhibit the activity of the antiporter
Na+/K+-ATPase (Li et
al., 1996; Handy et al.,
2002). In the amphibian heart, inhibition of
Na+/K+-ATPase by ouabain also induces a strong
activation of p38-MAPK (Stathopoulou et
al., 2006), indicating that copper could stimulate the kinase
through this mechanism.
Hsp27, the well-known downstream member of the p38-MAPK signalling pathway
(Kyriakis and Avruch, 2001),
was also investigated. This protein is implicated in cytoprotection since it
interacts with and stabilizes F-actin fibers under stressful conditions and
inhibits the mitochondrial apoptotic pathway by preventing cytochrome
c release (Guay et al.,
1997; Paul et al.,
2002; Concannon et al.,
2003). CuCl2, at either 25°C or 42°C, induced a
strong Hsp27 phosphorylation (Figs
2,
5), but did not activate
caspase-3 (Fig. 8). Hsp27
phosphorylation follows a similar pattern as the one for p38-MAPK when hearts
were perfused with increasing doses of CuCl2
(Fig. 2) and is p38-MAPK
dependent as exemplified with experiments using the kinase's specific
inhibitor SB203580 (Fig. 3).
However, no additive response was observed in the case of the simultaneous use
of CuCl2 and hyperthermia (Fig.
5), possibly because hyperthermia on its own is quite a strong
activator of Hsp27.
In conclusion, our results demonstrate that in Rana ridibunda heart, CuCl2 differentially activates the p38-MAPK signalling pathway depending on temperature. Overall, this p38-MAPK cascade activation seems to be beneficial for cardiac myocytes since it is associated with the motivation of protective cellular mechanisms, like that of the small Hsp27.
List of abbreviations
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Acknowledgments |
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References |
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TOPSummaryIntroductionMaterials and methodsResultsDiscussionReferences |
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Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I. (2001a). Activation of multiple MAPK pathways (ERKs, JNKs and p38-MAPK) by diverse stimuli in the amphibian heart. Mol. Cell. Biochem. 221,63 -69.[CrossRef][Medline]
Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I. (2001b). Stimulation of multiple MAPK pathways by mechanical overload in the perfused amphibian heart. Am. J. Physiol. 281,R1689 -R1698.
Aggeli, I.-K. S., Gaitanaki, C., Lazou, A. and Beis, I.
(2002). Hyperosmotic and thermal stress activate p38-MAPK in the
perfused amphibian heart. J. Exp. Biol.
205,443
-454.
Aggeli, I.-K. S., Gaitanaki, C. and Beis, I. (2006). Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2 cells. Cell. Signal. 18,1801 -1812.[CrossRef][Medline]
Bagnyukova, T. V., Storey, K. B. and Lushchak, V. I. (2003). Induction of oxidative stress in Rana ridibunda during recovery from winter hibernation. J. Therm. Biol. 28,21 -28.[CrossRef]
Bogoyevitch, M. A. (2000). Signalling via
stress-activated mitogen-activated protein kinases in the cardiovascular
system. Cardiovasc. Res.
45,826
-842.
Burlando, B., Magnelli, V., Panfoli, I., Berti, E. and Viarengo, A. (2003). Ligand-independent tyrosine kinase signalling in RTH 149 trout hepatoma cells: comparison among heavy metals and pro-oxidants. Cell. Physiol. Biochem. 13,147 -154.[CrossRef][Medline]
Concannon, C. G., Gorman, A. M. and Samali, A. (2003). On the role of Hsp27 in regulating apoptosis. Apoptosis 8,61 -70.[CrossRef][Medline]
Gaetke, L. M. and Chow, C. K. (2003). Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 189,147 -163.[CrossRef][Medline]
Gaitanaki, C., Stathopoulou, K., Stavridou, C. and Beis, I.
(2003). Oxidative stress stimulates multiple MAPK signalling
pathways and the phosphorylation of the small Hsp27 in the perfused amphibian
heart. J. Exp. Biol.
206,2759
-2769.
Gaitanaki, C., Papatriantafyllou, M., Stathopoulou, K. and Beis, I. (2006). Effects of various oxidants and antioxidants on the p38-MAPK signalling pathway in the perfused amphibian heart. Mol. Cell. Biochem. 291,107 -117.[CrossRef][Medline]
Giordano, F. J. (2005). Oxygen, oxidative stress, hypoxia and heart failure. J. Clin. Invest. 115,500 -508.[CrossRef][Medline]
Gius, D., Mattson, D., Bradbury, C. M., Smart, D. K. and Spitz, D. R. (2004). Thermal stress and the disruption of redox-sensitive signalling and transcription factor activation: possible role in radiosensitization. Int. J. Hyperthermia 20,213 -223.[CrossRef][Medline]
Greenway, S. C. and Storey, K. B. (2000). Activation of mitogen-activated protein kinases during natural freezing and thawing in the wood frog. Mol. Cell. Biochem. 209, 29-37.[CrossRef][Medline]
Guay, J., Lambert, H., Gingras-Breton, G., Lavoie, J. N., Huot, J. and Landry, J. (1997). Regulation of actin filament dynamics by p38 MAP kinase-mediated phosphorylation of heat shock protein 27. J. Cell Sci. 110,357 -368.[Abstract]
Gutteridge, J. M. (1985). Superoxide dismutase inhibits the superoxide-driven Fenton reaction at two different levels. Implications for a wider protective role. FEBS Lett. 185, 19-23.[CrossRef][Medline]
Handy, R. D., Eddy, F. B. and Baines, H. (2002). Sodium-dependent copper uptake across epithelia: a review of rationale with experimental evidence from gill and intestine. Biochim. Biophys. Acta 1566,104 -115.[Medline]
Hermes-Lima, M. and Storey, K. B. (1996). Relationship between anoxia exposure and antioxidant status in the frog Rana pipiens. Am. J. Physiol. 271,R918 -R925.
Hermes-Lima, M. and Storey, K. B. (1998). Role of antioxidant defences in the tolerance of severe dehydration by anurans. The case of the leopard frog Rana pipiens. Mol. Cell. Biochem. 189,79 -89.[CrossRef][Medline]
Hoffman, J. and Katz, U. (1997). Salt and water balance in the toad Bufo viridis during recovery from two different osmotically stressful conditions. Comp. Biochem. Physiol. 117A,147 -154.[CrossRef]
Hutchison, V. H. and Dupr, R. K. (1992). Thermoregulation. In Environmental Physiology of the Amphibians (ed. M. E. Feder and W. W. Burggren), pp.206 -249. Chicago: University of Chicago Press.
Jeon, K. I., Jeong, J. Y. and Jue, D. M.
(2000). Thiol-reactive metal compounds inhibit NF-
B
activation by blocking I kappa B kinase. J. Immunol.
164,5981
-5989.
Katz, U., Pagi, D., Hayat, S. and Degani, G. (1986). Plasma osmolarity, urine composition and tissue water content of the toad Bufo viridis Laur. in nature and under controlled laboratory conditions. Comp. Biochem. Physiol. 85A,703 -713.[Medline]
Kefaloyianni, E., Gourgou, E., Ferle, V., Kotsakis, E.,
Gaitanaki, C. and Beis, I. (2005). Acute thermal stress and
various heavy metals induce tissue-specific pro- or anti-apoptotic events
via the p38-MAPK signal transduction pathway in Mytilus
galloprovincialis (Lam.) J. Exp. Biol.
208,4427
-4436.
Kyriakis, J. M. and Avruch, J. (2001).
Mammalian mitogen-activated protein kinase signal transduction pathways
activated by stress and inflammation. Physiol. Rev.
81,807
-869.
Letelier, M. E., Lepe, A. M., Faundez, M., Salazar, J., Marin, R., Aracena, P. and Speisky, H. (2005). Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity. Chem. Biol. Interact. 151, 71-82.[CrossRef][Medline]
Li, J., Lock, R. A. C., Klaren, P. H. M., Swarts, H. G. P., Schuurmans Stekhoven, F. M. A. H., Wendelaar Bonga, S. E. and Flik, G. (1996). Kinetics of Cu2+ inhibition of Na+/K+-ATPase. Toxicol. Lett. 87, 31-38.[CrossRef][Medline]
Li, Z., Carter, J. D., Dailey, L. A. and Huang, Y. C. (2005). Pollutant particles produce vasoconstriction and enhance MAPK signaling via angiotensin type I receptor. Environ. Health Perspect. 113,1009 -1014.[Medline]
Lillywhite, H. B. (1971). Temperature selection by the bullfrog, Rana catesbeiana. Comp. Biochem. Physiol. 40A,213 -227.[Medline]
Linder, M. C. and Hazegh-Azam, M. (1996).
Copper biochemistry and molecular biology. Am. J. Clin.
Nutr. 63,797S
-811S.
Liochev, S. I. and Fridovich, I. (2002).
Copper, zinc superoxide dismutase and H2O2. Effects of
bicarbonate on inactivation and oxidations of NADPH and urate, and on
consumption of H2O2. J. Biol.
Chem. 277,34674
-34678.
Liochev, S. I. and Fridovich, I. (2006). The role of CO2 in metal-catalyzed peroxidations. J. Inorg. Chem. 100,694 -696.
Papadimitriou, E. A. and Loumbourdis, N. S. (2003). Copper kinetics and hepatic metallothionein levels in the frog Rana ridibunda, after exposure to CuCl2. Biometals 16,271 -277.[CrossRef][Medline]
Paul, C., Manero, F., Gonin, S., Kretz-Remy, C., Virot, S. and
Arrigo, A. P. (2002). Hsp27 as a negative regulator of
cytochrome c release. Mol. Cell. Biol.
22,816
-834.
Rouse, J., Cohen, P., Trigon, S., Morange, M., Alonso-Llamazares, A., Zamanillo, D., Hunt, T. and Nebreda, A. R. (1994). A novel kinase cascade triggered stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78,1027 -1037.[CrossRef][Medline]
Salo, D. C., Donovan, C. M. and Davies, K. J. (1991). HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. Free Radic. Biol. Med. 11,239 -246.[CrossRef][Medline]
Samet, J. M., Graves, L. M., Quay, J., Dailey, L. A., Devlin, R. B., Ghio, A. J., Wu, W., Bromberg, P. A. and Reed, W. (1998). Activation of MAPKs in human bronchial epithelial cells exposed to metals. Am. J. Physiol. 275,L551 -L558.
Schiaffonati, L., Rappociolo, E., Tacchini, L., Cairo, G. and Bernelli-Zazzera, A. (1990). Reprogramming of gene expression in postischemic rat liver: induction of proto-oncogenes and hsp 70 gene family. J. Cell. Physiol. 143, 79-87.[CrossRef][Medline]
Shi, X. L. and Dalal, N. S. (1992). The role of superoxide radical in chromium (VI)-generated hydroxyl radical: the Cr (VI) Haber-Weiss cycle. Arch. Biochem. Biophys. 292,323 -327.[CrossRef][Medline]
Shoemaker, V. H., Baker, M. A. and Loveridge, J. P. (1989). Effect of water balance on thermoregulation in waterproof frogs (Chiromantis and Phyllomedusa). Physiol. Zool. 62,133 -146.
Singh, K. P. and Sinha, R. C. (1990). Variation of ascorbic acid content in the different tissues of the frog Rana tigrina as a function of season. Jpn. J. Physiol. 40,435 -441.[CrossRef][Medline]
Solomon, E. I. and Lowery, M. D. (1993).
Electronic structure contributions to function in bioinorganic chemistry.
Science 259,1575
-1581.
Stathopoulou, K., Gaitanaki, C. and Beis, I.
(2006). Extracellular pH changes activate the p38-MAPK signalling
pathway in the amphibian heart. J. Exp. Biol.
209,1344
-1354.
Stokoe, D., Engel, K., Campbell, D. G., Cohen, P. and Gaestel, M. (1992). Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins. FEBS Lett. 313,307 -313.[CrossRef][Medline]
Turner, N. A., Xia, F., Azhar, G., Zhang, X., Liu, L. and Wei, J. Y. (1998). Oxidative stress induces DNA fragmentation and caspase activation via the c-Jun NH2-terminal kinase pathway in H9c2 cardiac muscle cells. J. Mol. Cell. Cardiol. 30,1789 -1801.[CrossRef][Medline]
Vassilopoulos, A., Gaitanaki, C., Papazafiri, P. and Beis, I. (2005). Atrial natriuretic peptide mRNA regulation by p38-MAPK in the perfused amphibian heart. Cell. Physiol. Biochem. 16,183 -192.[CrossRef][Medline]
Woessmann, W., Meng, Y.-H. and Mivechi, N. F. (1999). An essential role for mitogen-activated protein kinases, ERKs, in preventing heat-induced cell death. J. Cell. Biochem. 74,648 -662.[CrossRef][Medline]
Wu, W., Graves, L. M., Jaspers, I., Devlin, R. B., Reed, W. and Samet, J. M. (1999). Activation of the EGF receptor signaling pathway in human airway epithelial cells exposed to metals. Am. J. Physiol. 277,L924 -L931.
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P<0.001 vs control value.
