humanin and Hypoxia

The discovery of humanin (HN/MTRNR2) 20 years ago blazed a trail to identifying mitochondrial derived peptides with biological function.. Humanin is associated with pro-survival, cytoprotective, anti-inflammatory, and anti-oxidative properties and may play a role in reducing neurodegenerative and metabolic disease progression. Although the role of humanin in vitro and in vivo laboratory models is well characterized, the regulation of humanin in natural models that encounter lethal cytotoxic and oxidative insults, as part of their natural history, require immediate research. In this review, we discuss the conservation of humanin-homologues across champion hibernators, anoxia and freeze-tolerant vertebrates and postulate on the putative roles of humanin in non-model species.. We hope characterization of humanin in animals that are naturally immune to cellular insults, that are otherwise lethal for non-tolerant species, will elucidate key biomarkers and cytoprotective pathways with therapeutic potential and help differentiate pro-survival mechanisms from cellular consequences of stress.

Topics: Animals; Cold-Shock Response; Hibernation; Humans; Hypoxia; Intracellular Signaling Peptides and Proteins; Nervous System Physiological Phenomena; Stress, Physiological

Mitochondria was long thought to be an "end function" organelle that regulated the metabolic flux and apoptosis in the cell. However, with the discovery of the mitochondrial peptide (MDP) humanin (HN/MTRNR2), the cytoprotective and pro-survival applications of MDPs have taken the forefront of therapeutic and diagnostic research. However, the regulation of humanin-like MDPs in natural model systems that can tolerate lethal environmental and cytotoxic insults remains to be investigated. Red-eared sliders are champion anaerobes that can withstand three continuous months of anoxia followed by rapid bouts of oxygen reperfusion without incurring cellular damage. Freshwater turtles employ extensive physiological and biochemical strategies to combat anoxia, with metabolic rate depression and a global enhancement of antioxidant and cytoprotective pathways being the two most important contributors. The main aim of this study was to uncover and characterize the humanin-homologue in freshwater turtles as well as investigate the differential regulation of humanin in response to short and long-term oxygen deprivation. In this study we have used de novo and homology-based protein modelling to elucidate the putative structure of humanin in red-eared sliders as well as an ELISA and western immunoblotting to confirm the protein abundance in the turtle brain and six peripheral tissues during control, 5 h, and 20 h anoxia (n = 4/group). We found that a humanin-homologue (TSE-humanin) is present in red-eared sliders and it may play a cytoprotective role against oxidative damage.

Topics: Adaptation, Physiological; Amino Acid Sequence; Animals; Brain; Fresh Water; Humans; Hypoxia; Intracellular Signaling Peptides and Proteins; Kidney; Liver; Mitochondria; Models, Molecular; Muscles; Myocardium; Oxidative Stress; Oxygen; Protein Conformation, alpha-Helical; Sequence Alignment; Spleen; Structural Homology, Protein; Turtles