Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells

Abstract

Abstract. The present study investigated whether there is an interaction between reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) during chemical hypoxia-induced injury in PC12 cells. The results of the present study showed that cobalt chloride (CoCl 2 ), a chemical hypoxia agent, markedly induced ROS generation and phosphorylation of p38MAPK, as well as neuronal injuries. N-acetylcysteine (NAC), a ROS scavenger, blocked CoCl 2 -induced phosphorylation of p38MAPK. In addition, SB203580, an inhibitor of p38MAPK attenuated not only CoCl 2 -induced activation of p38MAPK, but also ROS production. These results suggest that ROS and p38MAPK are capable of interacting positively during chemical hypoxia. Furthermore, NAC and SB203580 markedly prevented CoCl 2 -induced cytotoxicity, apoptosis and a loss of mitochondrial membrane potential. Taken together, our findings suggest that the positive interaction between CoCl 2 induction of ROS and p38MAPK activation may play a significant role in CoCl 2 -induced neuronal injuries. We provide new insights into the mechanisms responsible for CoCl 2 -induced injuries in PC12 cells.

Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma

“…To investigate the key factors involved in oxidative stress promoting EV release, we first evaluated secreted EV concentration under different ROS levels. Our study utilized hydrogen peroxide (H 2 O 2 ) treated cells, a CoCl 2 hypoxia model (Lan et al., 2012 ), and a stable HBV replication model (HepG2.2.15 cell line) (Yuan et al., 2016 ) as high ROS conditions, while the ROS scavenger N‐acetyl cysteine (NAC) was used to abolish increased ROS (Figure S1a‐c ). Nanoparticle tracking analysis (NTA) (Figure 1a‐c ) and changes in EV markers (Figure 1d‐f ) revealed that oxidative stress promotes EV release in HCC cells.…”

Impact of HIF1-α/TGF-β/Smad-2/Bax/Bcl2 Pathways on Cobalt chloride-induced Cardiac and Hepatorenal Dysfunction

“…CoCl 2 is a well-known chemical that mimics hypoxia; it causes the same effects in several aspects in various cultured cells, including loss of mitochondrial membrane potential, increase the release of ROS that causes cell death, and increased expression of HIF-1α and p53, which are implicated in the apoptotic pathway [ 15 ].…”

“…CoCl 2 significantly increased the production of ROS, phosphorylated p38 mitogen-activated protein kinase (MAPK), and damaged neurons [ 15 ]. It has been suggested that the ROS produced by cobalt chloride have a role in the signaling mechanism that stabilizes the transcription factor HIF-1α during hypoxia.…”

Acetylated Chitosan Oligosaccharides Act as Antagonists against Glutamate-Induced PC12 Cell Death via Bcl-2/Bax Signal Pathway

“…ROS is a well known etiological factor associated with oxidative stress leading to cell death via apoptosis in a variety of cell types [ 37 , 38 , 39 , 40 ], and such effects can be blocked or delayed by a wide variety of antioxidants [ 41 ]. Mitochondria-dependent apoptotic pathways are involved in glutamate-induced cytotoxicity in PC 12 cells [ 42 ].…”