ArticleApoptosis : an international journal on programmed cell death2015
The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs.
Article in Apoptosis : an international journal on programmed cell death, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 47 citations in OpenAlex.
- Mitochondrial derived peptide humanin improved semen quality, semen freezability, antioxidant status and in-vitro fertility in crossbred bull.Scientific reports · 2026Article
- A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders.Protein and peptide letters · 2025Review
- Humanin Treatment Protects Against Venetoclax-Induced Bone Growth Retardation inJournal of the Endocrine Society · 2024Article
- Effects ofHuman reproduction open · 2024Article
- Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer.Current radiopharmaceuticals · 2024Observational
- Transcriptome Studies Reveal theAnimals : an open access journal from MDPI · 2023Article
- Article
- Mitochondria-derived peptides in aging and healthspan.The Journal of clinical investigation · 2022Review
- 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
- Effects of Mitochondrial-Derived Peptides (MDPs) on Mitochondrial and Cellular Health in AMD.Cells · 2020Review
- 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 analog enhances the protective effect of dexrazoxane against doxorubicin-induced cardiotoxicity.American journal of physiology. Heart and circulatory physiology · 2018Article
- Humanin: Functional Interfaces with IGF-I.Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society · 2016Review
- Article
- The Potent Humanin Analogue (HNG) Protects Germ Cells and Leucocytes While Enhancing Chemotherapy-Induced Suppression of Cancer Metastases in Male Mice.Endocrinology · 2015Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Human (HN) prevents stress-induced apoptosis in many cells/tissues. In this study we showed that HN ameliorated chemotherapy [cyclophosphamide (CP) and Doxorubicin (DOX)]-induced male germ cell apoptosis both ex vivo in seminiferous tubule cultures and in vivo in the testis. HN acts by several putative mechanisms via binding to: an IL-12 like trimeric membrane receptor; BAX; or insulin-like growth factor binding protein-3 (IGFBP-3, a proapoptotic factor). To understand the mechanisms of HN on male germ cell apoptosis, we studied five HN analogues including: HNG (HN-S14G, a potent agonist), HNG-F6A (no binding to IGFBP-3), HN-S7A (no self-dimerization), HN-C8P (no binding to BAX), and HN-L12A (a HN antagonist) on CP-induced male germ cell apoptosis in mice. CP-induced germ cell apoptosis was inhibited by HN, HNG, HNG-F6A, HN-S7A, and HN-C8P (less effective); but not by HN-L12A. HN-L12A, but not HN-S7A or HN-C8P, blocked the protective effect of HN against CP-induced male germ cell apoptosis. HN, HN-S7A, and HN-C8P restored CP-suppressed STAT3 phosphorylation. These results suggest that HN: (1) decreases DOX (ex vivo) and CP (in vivo) induced male germ cell apoptosis; (2) action is mediated by the membrane receptor/STAT3 with minor contribution by BAX-binding pathway; (3) self-dimerization or binding to IGFBP-3 may not be involved in HN's effect in testis. HN is an important molecule in the regulation of germ cell homeostasis after injury and agonistic analogues may be developed for treating male infertility or protection against chemotherapy side effects.
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