Oxidative stress is a key contributor to cellular damage. Mild stressors can trigger an adaptive response known as the preapoptotic cellular stress response (PACOS), which enhances cellular resistance to subsequent stress insults. PACOS has been described in rat hepatocytes. In this dissertation, we investigated the signaling pathways involved in primary hepatocytes and examined the occurrence of PACOS in rat cortical neurons. Additional attention was given to the interaction between PACOS and the unfolded protein response (UPR), both of which play crucial roles in cellular survival under hypoxia, ischemia, inflammation, and nutrient deprivation. Experimental work included in vitro cultures of primary hepatocytes from fed and fasted rats, as well as embryonic rat neurons. By using pharmacological stressors and modulating hydrogen peroxide production, we monitored caspase activation and thus resistance to apoptosis. By applying mild physiological stress (fasting), we investigated differences in cellular redox status, activation of signaling pathways, including caspase activation, expression of pro- and anti-apoptotic genes, and UPR markers. We confirmed that PACOS inhibits apoptosis by suppressing caspase-9 activation, thereby increasing cellular resilience to secondary stress. The results demonstrated significant differences between cells from fed and fasted animals, further underscoring the influence of metabolic state on the stress response. Hepatocytes from fasted animals had more robust protective mechanisms and a stronger expression of anti-apoptotic genes. By modulating caspase activity in embryonic neurons, we also demonstrated that PACOS is not restricted to hepatocytes. The results highlight PACOS as a protective mechanism that can be induced by physiological stressors such as fasting and contribute to a better understanding of its potential in mitigating liver and other tissue damage.
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