Pathways of cell signaling in hyperoxia

Normobaric Hyperoxia Delays Perfusion/Diffusion Mismatch Evolution, Reduces Infarct Volume, and Differentially Affects Neuronal Cell Death Pathways after Suture Middle Cerebral Artery Occlusion in Rats

“…These data indicate that the observed cytoprotective properties of NBO in the ischemic brain are not determined by caspase-3-mediated pathways of apoptosis. Normobaric hyperoxia treatment appeared to induce such apoptotic pathways in nonischemic brain tissue, corroborating previous studies that showed hyperoxia-induced cell death through caspase-3 activation (Gerstner et al, 2006;Lee and Choi, 2003). In light of decreased penumbral caspase-8 cleavage with NBO (Liu et al, 2006), it can be speculated that treatment with NBO only delays initiation of early stages of apoptosis but ultimately cannot prevent cell death (Wang and Lenardo, 2000).…”

“…Interestingly, we found more ISEL-positive cells in nonischemic hemisphere ROIs of NBO-treated animals relative to air-treated controls. Different, potentially interacting pathophysiological mechanisms may be responsible for the observed contralesional neuronal damage, including hypotension and transsynaptic effects (Zhu and Auer, 1995) as well as direct cytotoxicity of oxygen such as hyperoxia-induced reactive oxygen species formation (Lee and Choi, 2003). The former two possibilities are remote given the apparently normal (i.e., > 80 mm Hg) mean arterial blood pressure in all animals as well as the relatively milder insult in NBO-treated animals compared with controls (Zhu and Auer, 1995).…”

“…In light of decreased penumbral caspase-8 cleavage with NBO (Liu et al, 2006), it can be speculated that treatment with NBO only delays initiation of early stages of apoptosis but ultimately cannot prevent cell death (Wang and Lenardo, 2000). Potentially, reactive oxygen speciesmediated mitochondrial damage could lead to caspase-9 activation, leading to cell death through effector caspases such as caspase-6 (Gerstner et al, 2006;Lee and Choi, 2003;Wang and Lenardo, 2000); however, further studies are necessary to confirm these hypotheses.…”

Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity

“…22,23 MEK and MKK are the upstream kinases for ERK1/2 and p38 MAPK, respectively. Recently, the MAP kinase pathways have been linked to hyperoxic toxicity in both cell cultures and animal models; 24,25 hyperoxia primarily activates ERK1/2 but less so p38. 25 Buckley et al have demonstrated that increased ERK1/2 may correlate with protection against hyperoxic toxicity in rats.…”

“…Recently, the MAP kinase pathways have been linked to hyperoxic toxicity in both cell cultures and animal models; 24,25 hyperoxia primarily activates ERK1/2 but less so p38. 25 Buckley et al have demonstrated that increased ERK1/2 may correlate with protection against hyperoxic toxicity in rats. 24,26,27 p38 MAPK is linked to mismatch repair DNA response via the G2 checkpoint and to resistance to chemotherapeutic DNA-methylating agents.…”