Phoenixin: a novel brain-gut-skin peptide with multiple bioactivity

Abstract

In this brief review we summarize the current fndings relative to the discovery of a small peptide ligand, phoenixin (PNX). Using a bioinformatic approach, two novel peptides PNX-14 and PNX-20 containing 14 and 20 amino acids, respectively, were isolated from diverse tissues including the brain, heart, lung and stomach. Mass spectrometry analysis identified a major and minor peak corresponding to PNX-14 and PNX-20, in rat or mouse spinal cord extracts. With the use of a rabbit polyclonal antiserum, phoenixin immunoreactivity (irPNX) was detected in discrete areas of the rodent brain including several hypothalamic subnuclei and dorsal motor nucleus of the vagus. In addition, irPNX was detected in a population of sensory ganglion cells including dorsal root ganglion, nodose ganglion and trigeminal ganglion, and in cell processes densely distributed to the superficial layers of the dorsal horn, nucleus of the solitary tract and spinal trigeminal tract. irPNX cell processes were also detected in the skin and myenteric plexus, suggesting a brain-gut and/or brain-skin connection. Pharmacological studies show that PNX-14 injected subcutaneously to the nape of the neck of mice provoked dose-dependent repetitive scratching bouts directed to the back of the neck with the hindpaws. Our result suggests that the peptide PNX-14 and/or PNX-20, may serve as one of the endogenous signal molecules transducing itch sensation. Additionally, results from other laboratories show that exogenous PNX may affect a number of diverse behaviors such as memory formation, depression, reproduction, food-intake and anxiolytic-like behaviors.

An Integral Approach for Understanding the Bioactive Small Molecules in Cardiovascular Diseases

“…A recent study showed that PNX was also expressed on the mammalian heart and served as a cardioprotective factor. Although it consisted of 20 amino acids, PNX was shown to reduce the contractility and relaxation of heart in vitro test, and it could inhibit apoptosis to narrow the infarct size and accelerate the recovery of contractility compared with the ischemia/reperfusion (I/R) treat alone [83,84], In addition, the experiments on the heart of obese rats showed the same result. All these evidences suggested that PNX was a novel regulating small molecule to exert in both the heart and metabolic disorders.…”

Regulation and physiological functions of phoenixin

“…In rat brain, nesfatin-1 showed a high degree of co-localization with phoenixin. Nearly one-fifth of cells in the PVN, Arc, ventromedial nucleus and lateral hypothalamic nucleus showed irPNX ( Lyu, et al, 2013 ; Lyu et al, 2018 ). Bioinformatic survey demonstrated that both phoenixin and nesfatin were as ancient neuropeptides with premetazoan origin ( Yanez-Guerra et al, 2022 ).…”

The GnRH analogues affect novel neuropeptide SMIM20/phoenixin and GPR173 receptor expressions in the female rat hypothalamic–pituitary–gonadal (HPG) axis

“…Moreover, the correlation between the increased plasma levels of PNX, LH, and androgen hormones suggests a possible role for the peptide in the development of human polycystic ovary syndrome (PCOS) . Even if additional physiological activity of PNX are known, such as in food intake control, the cardiovascular system, and in skin, the predominant idea is that PNX plays a crucial role in the modulation of the HPG axis with a significant relapse in reproduction, that may be potentially useful in translational medicine.…”