ArticleThe Journal of biological chemistry2010
Interaction of insulin-like growth factor-binding protein-3 and BAX in mitochondria promotes male germ cell apoptosis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- IGFBP3 modulation of tumor pathogenesis and cell signaling pathways (Review).Oncology letters · 2025Review
- ThroughoutFrontiers in endocrinology · 2023Article
- Roles of IGFBP-3 in cell migration and growth in an endophytic tongue squamous cell carcinoma cell line.Scientific reports · 2022Article
- Insulin-like growth factor binding protein 3 promotes radiosensitivity of oral squamous cell carcinoma cells via positive feedback on NF-κB/IL-6/ROS signaling.Journal of experimental & clinical cancer research : CR · 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
- Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): Unraveling the Role in Mediating IGF-Independent Effects Within the Cell.Frontiers in cell and developmental biology · 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
- Mechanisms of Heshouwuyin in regulating apoptosis of testicular cells in aging rats through mitochondrial pathway.BMC complementary and alternative medicine · 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
- The effects of humanin and its analogues on male germ cell apoptosis induced by chemotherapeutic drugs.Apoptosis : an international journal on programmed cell death · 2015Article
- Effects of portulacerebroside a on apoptosis of human leukemia HL60 cells and p38/JNK signaling pathway.International journal of clinical and experimental pathology · 2015Article
- Insulin-like growth factor binding protein-3 (IGFBP-3): Novel ligands mediate unexpected functions.Journal of cell communication and signaling · 2013Article
- The cytoprotective peptide humanin is induced and neutralizes Bax after pro-apoptotic stress in the rat testis.Andrology · 2013Article
- Elevated IGFBP3 levels in diabetic tears: a negative regulator of IGF-1 signaling in the corneal epithelium.The ocular surface · 2012Article
- New insight into the molecular mechanisms of the biological effects of DNA minor groove binders.PloS one · 2011Article
- Nuclear export and mitochondrial and endoplasmic reticulum localization of IGF-binding protein 3 regulate its apoptotic properties.Endocrine-related cancer · 2010Article
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9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Germ cell apoptosis is crucial for spermatogenesis and can be triggered by various stimuli, including intratesticular hormone deprivation. This study proposes a role for insulin-like growth factor binding protein-3 (IGFBP-3) in male germ cell apoptosis. Groups of adult Sprague-Dawley male rats received one of the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of the gonadotropin-releasing hormone antagonist (GnRH-A), acyline, on day 1 and a daily IT injection of saline; (iii) daily IT injection of IGFBP-3; and (iv) a GnRH-A injection on day 1 and a daily IT injection of IGFBP-3. Germ cell apoptosis increased significantly after IGFBP-3 or GnRH-A treatment which was further enhanced by the combined treatment. After co-immunoprecipitation with BAX antibody, IGFBP-3 association with BAX was demonstrated in total and mitochondrial fractions but not in the cytosol of testis extracts. BAX-associated IGFBP-3 expression was increased in mitochondria after treatment compared with control, which was confirmed by an IGFBP-3 enzyme-linked immunosorbent assay. Dot blot studies further validated the BAX-IGFBP-3 binding in vitro. IGFBP-3 as well as BAX induced release of cytochrome c and DIABLO from isolated testicular mitochondria in vitro. IGFBP-3, when combined with an ineffective dose of BAX, triggered release of these proteins from isolated mitochondria at a 4-fold lower dose than IGFBP-3 alone. Our data demonstrate that the IGFBP-3 and BAX interaction activates germ cell apoptosis via the mitochondria-dependent pathway. This represents a novel pathway regulating germ call homeostasis that may have significance for male fertility and testicular disease.
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