ArticleAndrology2013
The cytoprotective peptide humanin is induced and neutralizes Bax after pro-apoptotic stress in the rat testis.
Article in Andrology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Mechanism of mitochondrial oxidative phosphorylation disorder in male infertility.Chinese medical journal · 2025Review
- Mitochondrial-derived peptides, HNG and SHLP3, protect cochlear hair cells against gentamicin.Cell death discovery · 2024Article
- Mitochondrial-derived peptides in cardiovascular disease: Novel insights and therapeutic opportunities.Journal of advanced research · 2024Review
- Emerging mitochondrial signaling mechanisms in cardio-oncology: beyond oxidative stress.American journal of physiology. Heart and circulatory physiology · 2022Review
- The Molecular Structure and Role of Humanin in Neural and Skeletal Diseases, and in Tissue Regeneration.Frontiers in cell and developmental biology · 2022Review
- Colivelin, a synthetic derivative of humanin, ameliorates endothelial injury and glycocalyx shedding after sepsis in mice.Frontiers in immunology · 2022Article
- Inducible fold-switching as a mechanism to fibrillate pro-apoptotic BCL-2 proteins.Biopolymers · 2021Article
- The IL-27 component EBI-3 and its receptor subunit IL-27Rα are essential for the cytoprotective action of humanin on male germ cells†.Biology of reproduction · 2021Article
- Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases.Frontiers in endocrinology · 2021Review
- Humanin selectively prevents the activation of pro-apoptotic protein BID by sequestering it into fibers.The Journal of biological chemistry · 2020Article
- Humanin induces conformational changes in the apoptosis regulator BAX and sequesters it into fibers, preventing mitochondrial outer-membrane permeabilization.The Journal of biological chemistry · 2019Article
- Mitochondrial Peptide Humanin Protects Silver Nanoparticles-Induced Neurotoxicity in Human Neuroblastoma Cancer Cells (SH-SY5Y).International journal of molecular sciences · 2019Article
- The humanin analogue (HNG) prevents temozolomide-induced male germ cell apoptosis and other adverse effects in severe combined immuno-deficiency (SCID) mice bearing human medulloblastoma.Experimental and molecular pathology · 2019Article
- Humanin is a novel regulator of Hedgehog signaling and prevents glucocorticoid-induced bone growth impairment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Humanin analog enhances the protective effect of dexrazoxane against doxorubicin-induced cardiotoxicity.American journal of physiology. Heart and circulatory physiology · 2018Article
- Humanin inhibits apoptosis in pituitary tumor cells through several signaling pathways including NF-κB activation.Journal of cell communication and signaling · 2017Article
- The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity.Scientific reports · 2017Article
- The Mitochondrial-Derived Peptide Humanin Protects RPE Cells From Oxidative Stress, Senescence, and Mitochondrial Dysfunction.Investigative ophthalmology & visual science · 2016Article
- The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice.Endocrinology · 2015Article
- Humanin protects against chemotherapy-induced stage-specific male germ cell apoptosis in rats.Andrology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
We have previously demonstrated that the mitochondria-derived cytoprotective peptide humanin (HN), when administered intratesticularly to rats, rescues germ cells from apoptosis secondary to testicular stress of hormonal deprivation induced by gonadotropin-releasing hormone antagonist (GnRH-A). To decipher the cellular mechanisms of HN action in the amelioration of GnRH-A-induced germ cell apoptosis, adult male rats received the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of GnRH-A on Day 1 and daily IT injection of saline; (iii) daily IT injection of synthetic HN; and (iv) GnRH-A injection on Day 1 and daily IT injection of HN (GnRH-A+HN). HN alone had no effect on germ cell apoptosis. GnRH-A increased germ cell apoptosis and BAX in the testicular mitochondrial fractions. Synthetic HN decreased germ cell apoptosis induced by GnRH-A and BAX in the mitochondria. We deduced that the cytoprotective action of synthetic HN on GnRH-A-induced germ cell apoptosis was mediated by attenuating p38 mitogen-activated protein kinase activity and increasing STAT3 phosphorylation. The effect of synthetic HN on the expression of endogenous rat HN in the testis was studied using rat HN specific antibody. GnRH-A treatment increased, but concomitant treatment with synthetic HN reduced endogenous rat HN expression in both cytosolic and mitochondrial fractions in testis. Co-immunoprecipitation experiments demonstrated that the increased rat HN was physically associated with BAX in the cytosolic testicular fractions after GnRH-A treatment. Double-immunofluorescence staining confirmed the co-localization of BAX and rat HN in the cytoplasm of Leydig cells and spermatocytes after GnRH-A treatment. We conclude that the cytoprotective effect of exogenously administered synthetic HN is mediated by interactions of endogenous rat HN with BAX in the cytoplasm preventing the entry of BAX to the mitochondria to govern the fate of germ cell survival or death during pro-apoptotic stress to the testis in rats.
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