CoCl2 induces protective eventsviathe p38-MAPK signalling pathway and ANP in the perfused amphibian heart

Abstract

RT-PCR). CoCl 2 treatment significantly increased ANP mRNA levels, whereas, in the presence of antioxidants, the transcript levels returned to basal values. All the above data indicate that CoCl 2 stimulates compensatory mechanisms involving the p38-MAPK signalling cascade along with ANP.Key words: CoCl 2 , hypoxia, frog heart, p38-MAPK, ANP, cardioprotection, oxidative stress, signalling. Summary 2268Nitric oxide (NO) is another member of the free radical family that diffuses rapidly and does not readily react with most biomolecules (Lancaster, 1994). However, NO reaction with O 2 -generates peroxynitrite (OONO -), which is highly cytotoxic (Beckman and Koppenol, 1996). Therefore, in the context of, for example, SOD competing with NO for binding to the superoxide anions, it becomes evident that SOD exerts its cardioprotective function by regulating formation of other ROS as well (peroxynitrite in this case). Given the interaction between these reactions one can deduce that, in this context, this is also the case for CAT.Oxidative stress (exemplified by perfusion with H 2 O 2 ) has also been found to transcriptionally upregulate atrial natriuretic peptide (ANP) levels in the amphibian heart (Vassilopoulos et al., 2005). There is also data implicating NO in the mechanism of this cardiac peptide hormone regulation (Sanchez-Ferrer et al., 1990; Carnio et al., 2004). Therefore, ANP appears to constitute another factor involved in the cardiac compensatory response to stimuli that could disturb extracellular fluid volume and electrolyte balance (Glass et al., 1996;Silberbach and Roberts, 2001), including redox perturbations.Oxidative stress may trigger activation of a plethora of signalling cascades (Kannan and Jain, 2000) including mitogen-activated protein kinase (MAPK) pathways (Feuerstein and Young, 2000). The three major subfamilies characterized in mammals are: the extracellular signalregulated kinases (ERKs), the c-jun N-terminal kinases (JNKs) and p38 reactivating kinase (p38-MAPK) (Kyriakis and Avruch, 2001;Pearson et al., 2001). The respective MAPKs have also been identified in the amphibian heart (Aggeli et al., 2001a). These kinases interact with their substrates in both the cytoplasm and the nucleus, transducing a variety of molecular signals (Bogoyevitch, 2000). Amphibian heart p38-MAPK, in particular, has been demonstrated to be activated by various forms of environmental stress, including mechanical and hyperosmotic as well as thermal (Aggeli et al., 2001b;Aggeli et al., 2002). Additionally, certain antioxidants (SOD and CAT) have been demonstrated to reverse H 2 O 2 -induced amphibian heart p38-MAPK activation (Gaitanaki et al., 2006a). H 2 O 2 -induced (oxidative stress) p38-MAPK interacts with MAPKactivated-protein-kinase 2 (MAPKAPK2), a kinase that subsequently phosphorylates the small heat shock protein Hsp27 (Gaitanaki et al., 2003). Phosphorylation of Hsp27 contributes to stabilization of the actin cytoskeleton, protecting cells against unfavourable stressful conditions (Paul et al., 2002; Con...

Melatonin attenuates apoptosis and mitochondrial depolarization levels in hypoxic conditions of SH-SY5Y neuronal cells induced by cobalt chloride (CoCl2)

“…Liu et al (2009) reported that hypoxia-induced apoptosis is related to p38MAPK activity in cultured rat cerebellar neurons. However, MAPK members can be activated by ROS products generated intracellularly, as well as by an exterior substance, such as H 2 O 2 administered (Banno et al, 2001;Gaitanaki et al, 2007;Chen et al, 2009Chen et al, , 2014. Our findings are consistent with those of the previous studies mentioned above and comparable with the recent evidence that the members of different proteins such as ERK1/2, p38MAPK, and MAPKs mediate neuronal apoptosis.…”

Cobalt chloride decreases EC-SOD expression through intracellular ROS generation and p38-MAPK pathways in COS7 cells

“…We further investigated the mechanisms that regulate EC-SOD expression. It has been reported that p38-MAPK, one of the MAPK family, is activated in hypoxic conditions by intracellular ROS [21]. Moreover, we have previously reported that the expression of EC-SOD is regulated by p38-MAPK in human smooth muscle cells stimulated by TNF-a [29].…”

“…From these results, we confirmed that the expression of EC-SOD is regulated through intracellular ROS generation. It has been reported that p38-MAPK is activated in hypoxic conditions and regulated by intracellular ROS [21]. We next investigated the effect of p38-MAPK on EC-SOD expression.…”

TGF-β₂- and H₂O₂-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

“…LA has been widely used as a therapeutic agent in diseases associated with increased oxidative stress [53]. A similar effect of LA could be observed in the perfused amphibian heart, in which oxidative stress-induced Hsp27 expression could be reduced by LA [54]. In contrast, LA-mediated cytoprotection against oxidative stress was accompanied by Hsp upregulation in primary neuronal cell cultures in vitro [55] and in the diabetic rat liver in vivo [56].…”

“…In contrast, LA-mediated cytoprotection against oxidative stress was accompanied by Hsp upregulation in primary neuronal cell cultures in vitro [55] and in the diabetic rat liver in vivo [56]. One explanation for these contrary effects of LA might be that high-dose LA can enhance Hsp expression by activating the transcriptional factor heat shock factor-1, while lower doses of LA reduce the expression of ROS-sensitive Hsp based on their antioxidant properties [51,53,54]. Thus, increased αB-crystallin and Hsp27 concentrations, as found in the ONH of glaucomatous eyes [3,4], may result from increased ROS production generated by TGF-β 2 and H 2 O 2 .…”