Anti‐apoptotic factor humanin is expressed in the testis and prevents cell‐death in leydig cells during the first wave of spermatogenesis

Abstract

Humanin (HN) is a 24 amino acids peptide with potent neuro-survival properties that protects against damage associated with Alzheimer's disease. In the present report, we have demonstrated by immunohistochemical analysis and Western blotting the pattern of expression of rat humanin (HNr) in the testis of 10- to 60-day-old rats. The Leydig cells of 10- and 40- day-old rats expressed this peptide at high levels; and in the testis of 60-day-old rats the expression of HNr expanded to include Leydig, endothelial, peritubular and germ cells. As monitored by Western blotting, HNr was released into the medium of cultures of Leydig cells isolated from 10-, 40-, and 60-days-old rats. HNr stimulated the incorporation of [(3)H]TdR into DNA of Leydig cells from 10-days-old rats, in a manner that indicated promotion of cell survival rather than an increase in the rate of cell multiplication. This peptide also enhanced steroidogenesis by cultured Leydig cells from 10- to 40-day-old rats both alone and synergistically with IGF-I. The expression of HNr in cultured Leydig cells increased in response to GH and IGF-I. In summary, we demonstrated here that HNr was expressed at all stages of maturation in the rat testis. This peptide promoted the survival of Leydig cells in culture and interacted with IGF-I to stimulate DNA synthesis and steroidogenesis. We propose that HNr is a novel testicular anti-apoptotic factor.

SH3-binding Protein 5 Mediates the Neuroprotective Effect of the Secreted Bioactive Peptide Humanin by Inhibiting c-Jun NH2-terminal Kinase

“…2-4 for review). Humanin also suppresses cell death in a variety of non-AD-related in vitro and in vivo cell death models; for example, serum deprivation-induced death of several cell types including PC12 neuronal cells (5), primary peripheral lymphocytes (6), K562 myeloblasts (7), and cultured islet ␤ cells (8), as well as death of Leydig cells during the first wave of spermatogenesis (9), ischemia-induced neuronal death in a mouse ischemic stroke model (10,11), gonadotropin-releasing hormone antagonist-induced death of testicular germ cells (12), ischemic death of myocardiocytes (13), and oxidized LDL-induced death of vascular endothelial cells (14). Humanin has other functions aside from inhibition of cell death.…”

Humanin: A novel functional molecule for the green synthesis of graphene

“…Since its initial discovery, several cDNAs with sequence homology to HN have been identified in plants, nematodes, and rodents, suggesting that the protein is evolutionarily conserved [49]. HN also plays a role in preventing cell death in tissues other than the nervous system [50].…”

Mitochondrial DNA Mutations May Contribute to Aging Via Cell Death Caused by Peptides that Induce CytochromecRelease

“…Furthermore, there is controversy whether the humanin peptide is normally expressed, in part because its coding sequence is embedded within the 16S rRNA gene. 42,43 The mouse mitochondrial genome likewise encodes a humanin homolog, raising the possibility that it might serve as a target for mutagenesis leading to the generation of a mutant peptide capable of promoting cytochrome c release. Mitochondria efficiently secrete peptides generated within the matrix of the organelle.…”