Citation

Cetaceans are a group of species that have adaptations and physiological responses to aquatic life, as well as a robust antioxidant defense system that allows them to mitigate the damage caused by ischemia/reperfusion cycles associated with diving. There is a greater understanding of the signaling cascades that characterize ischemic inflammation in humans than in cetaceans, and, in turn, the molecular and biochemical mechanisms associated with the physiological adaptations of cetaceans to tolerate inflammatory events are not fully understood. Heme oxygenase (HO) is a cytoprotective protein and is involved in the anti-inflammatory response. HO catalyzes the first step in the oxidative degradation of the heme group. The inducible isoform HO-1 is regulated by several stimuli, including hypoxia, oxidative stress, and inflammatory mediators. The objective of this study was to characterize the HO-1 of bottlenose dolphins (Tursiops truncatus) in silico and compare its structure with that of terrestrial mammals, as well as to evaluate the response of HO-1 and proinflammatory cytokines (IL-1?, IL-6 and TNF-?) in response to proinflammatory challenges in leukocytes of bottlenose dolphins compared to leukocytes of humans. The upstream sequence of HO-1 was obtained from the NCBI and Ensemble databases, and the structure of the gene was determined with bioinformatics tools. Five exons and four introns were identified, and proximal regulatory elements were detected in the upstream region. The 'fingerprint' of HO-1 and His-25 was found to be highly conserved in the species analyzed. Amino acid sequence alignment and evidence of negative selection suggest that HO-1 is a conserved protein. However, amino acids with different rotation were found at the active site of the bottlenose dolphin molecule. In leukocytes isolated from humans and bottlenose dolphins, the effect of lipopolysaccharide (LPS) on the expression of the IL-1?, IL-6, TNF-?, HMOX1 and GAPDH genes, the levels of IL-1?, IL-6, and TNF-?, as well as the enzymatic activity of HO, was experimentally determined. In human leukocytes a classic proinflammatory response was found, while in leukocytes of bottlenose dolphins the response was attenuated. A significant increase in HO activity (p