Acute hypoxia elevates arginase 2 and induces polyamine stress response in zebrafish via evolutionarily conserved mechanism

Abstract

Living organisms repeatedly encounter stressful events and apply various strategies to survive. Polyamines are omnipresent bioactive molecules with multiple functions. Their transient synthesis, inducible by numerous stressful stimuli, is termed the polyamine stress response. Animals developed evolutionarily conserved strategies to cope with stresses. The urea cycle is an ancient attribute that deals with ammonia excess in terrestrial species. Remarkably, most fish retain the urea cycle genes fully expressed during the early stages of development and silenced in adult animals. Environmental challenges instigate urea synthesis in fish despite substantial energetic costs, which poses the question of the urea cycle's evolutionary significance. Arginase plays a critical role in oxidative stress-dependent reactions being the final urea cycle enzyme. Its unique subcellular localization, high inducibility, and several regulation levels provide a supreme ability to control the polyamine synthesis rate. Notably, oxidative stress instigates the arginase-1 activity in mammals. Arginase is also dysregulated in aging organisms' brain and muscle tissues, indicating its role in the pathogenesis of age-associated diseases. We designed a study to investigate the levels of the urea cycle and polyamine synthesis-related enzymes in a fish model of acute hypoxia. We evidence synchronized elevation of arginase-2 and ornithine decarboxylase following oxidative stress in adult fish and aging animals signifying the specific function of arginase-2 in fish. Moreover, we demonstrate oxidative stress-associated polyamine synthesis' induction and urea cycle' arrest in adult fish. The subcellular arginase localization found in the fish seems to correspond to its possible evolutionary roles.

Synergistic effect of spermidine and ciprofloxacin against Alzheimer disease in male rat via ferroptosis modulation

“…(Polis et al, 2018). Our result is in accordance with the results of (Banerjee et al, 2022) who reported that arginaseI dysregulated in aged brain, suggesting their role in the pathogenesis of age-related diseases. These elevated levels were signi cantly decrease upon co treatment with SPD or CPFX with minimal diminish in the SPD-CPFX combination group and this result was similar to the results obtained by (Avtandilyan et al, 2013) who demonstrate that SPD in uence exactly on the special stereospeci c regulatory site of arginase .Thus, the change of arginase activity could be a consequence of quantitative changes of polyamines.…”

“…Data are presented as mean ± SEM (standard error of mean), n = 8 per group. Mean values with different superscript letters in the same column are signi cantly different at (p≤0.05).Table(5): Histopathological score of hippocampal sections of different experimental groups…”

Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection

“…Physical, chemical, or emotional stress (207,208) triggers a brain polyamine stress response resulting in an increased polyamine synthesis that is marked by higher expression of arginase 2 and ODC (209). Initially, this response is protective, as transient upregulation is associated with cell survival, but prolonged activation leads to polyamine accumulation and induces chronic stress that is linked to neurodegeneration (207,210).…”

Versatile roles of polyamines in improving abiotic stress tolerance of plants

“… Gilad and Gilad (2003) coined the term polyamine stress response (PSR), which is a common reaction to stressful stimuli, including physical, emotional, and hormonal stressors, with a magnitude related to stress intensity. It is universally accepted that transient polyamines synthesis is induced in various species (not just in plants) by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response ( Banerjee et al., 2021 ), which was observed in fish and mammals. Thus, it is ubiquitous and universal.…”