Description
Humanin is a naturally occurring micropeptide transcribed directly from the 16S ribosomal RNA region of the mitochondrial genome (mtDNA). Originally identified during genomic screens for factors that rescue neurons from familial Alzheimer’s disease mutants, Humanin has since been recognized in experimental pharmacology as a highly pleiotropic, broad-spectrum survival factor.
In laboratory settings, synthetic Humanin is utilized as a chemical probe to study cellular resilience, mitochondrial stress responses, and targeted apoptosis evasion. Because it is capable of operating through both intracellular protein-protein interactions and extracellular receptor binding, researchers employ this peptide across diverse mammalian models to investigate the buffering of amyloid-beta (Aβ) toxicity, the suppression of reactive oxygen species (ROS), and the modulation of the IGF-1 metabolic axis.
Biochemical Characteristics
Chemically, Humanin is an amphipathic polypeptide engineered to maintain robust stability while interacting with cytosolic apoptotic mediators and complex membrane receptors.
- Sequence/Structure: 24-amino acid polypeptide; Met-Ala-Pro-Arg-Gly-Phe-Ser-Cys-Leu-Leu-Leu-Leu-Thr-Ser-Glu-Ile-Asp-Leu-Pro-Val-Lys-Arg-Arg-Ala.
- Receptor Affinity: Extracellularly, it binds to the G protein-coupled receptor formyl peptide receptor-like 1 (FPRL1/FPR2) and the trimeric ciliary neurotrophic factor receptor (CNTFR)/WSX-1/gp130 complex. Intracellularly, it acts as a direct binding partner to the pro-apoptotic protein BAX and IGFBP-3.
- Stability: Supplied as a lyophilized salt to ensure structural integrity and prevent hydrolytic degradation during long-term storage.
- Specificity: Uniquely acts to prevent catastrophic cellular apoptosis without inducing unregulated hyperplastic tissue growth or cellular proliferation, making it an essential reagent in geroprotection and neurobiology assays.
Chemical Properties
| Property |
Specification |
| Molecule Name |
Humanin |
| Synonyms |
HN; Mitochondrial-derived peptide HN; MTRNR2-encoded peptide |
| Molecular Formula |
C119H204N34O32S2 |
| Molecular Weight |
2687.2 g/mol |
| Form |
Lyophilized Powder |
| Purity |
≥99% (Verified via HPLC) |
| Solubility |
Soluble in water and aqueous buffers (refer to SDS) |
| Documentation |
COA available per lot; SDS available |
Humanin is strictly for laboratory research and is commonly employed in the following investigational areas:
Neurodegeneration and Amyloid-Beta Toxicity
Humanin is a foundational reagent in neurobiological models of Alzheimer’s disease. Researchers apply the peptide to cultured neurons to quantify its ability to suppress neurotoxicity induced by various amyloid-beta fragments, preserving synaptic plasticity and completely preventing early-stage caspase activation.
Mitochondrial Bioenergetics and Apoptosis
In experimental models of hypoxia, ischemia, and starvation, Humanin is used to map intrinsic apoptotic pathways. Assays focus on how the peptide’s direct physical interaction with BAX prevents mitochondrial membrane permeabilization, thereby preserving ATP production and oxidative phosphorylation efficiency under extreme distress.
Metabolic Homeostasis and Glucoregulation
Physiological studies employ Humanin to observe its regulatory effects on metabolism and the endocrine system. Researchers evaluate its capacity to interact with the IGF-1/IGFBP-3 axis to improve hypothalamic insulin sensitivity, regulate hepatic glucose output, and normalize systemic energy expenditure.
Cardiovascular Ischemia and Endothelial Function
Due to its profound cytoprotective traits, Humanin is widely investigated in cardiovascular models. Experimental protocols assess its utility in reducing myocardial infarct size, mitigating oxidative damage in cardiomyocytes, and preventing oxidized LDL-induced apoptosis in human endothelial cells.
Pathway / Mechanistic Context
The primary mechanism of action for Humanin in research settings is dual-modal, orchestrating survival through both direct intracellular binding and extracellular signal transduction.
- Intracellular BAX Antagonism: Within the cytosol, Humanin directly binds to the pro-apoptotic protein BAX. This interaction physically prevents BAX from oligomerizing and translocating to the mitochondrial membrane, halting the release of cytochrome c and terminating the intrinsic apoptotic cascade.
- Extracellular Receptor Activation: Secreted Humanin functions as a ligand for the GPCR FPR2 or the CNTFR/WSX-1/gp130 complex. Binding triggers the phosphorylation and activation of the JAK2/STAT3 and ERK1/2 MAPK signaling cascades, which profoundly upregulate survival gene transcription.
- Resulting Flux: The combination of neutralizing mitochondrial collapse and upregulating extracellular survival signaling creates a cytoprotective shield. This dual action preserves cellular viability across a wide spectrum of stress states, including neurotoxicity, severe oxidative stress, and nutrient deprivation.
Preclinical Research Summary
Published preclinical literature documents investigations of Humanin across multiple distinct experimental models:
- Cognitive Preservation: In transgenic rodent models expressing human Alzheimer’s mutations, exogenous administration of Humanin successfully attenuated spatial memory deficits and significantly reduced the localized accumulation of neurotoxic amyloid plaques.
- Cardioprotection: Research demonstrates that pretreatment with Humanin during experimental myocardial ischemia-reperfusion injury drastically reduces cardiac apoptosis, preserves left ventricular hemodynamics, and inhibits reactive oxygen species (ROS) production.
- Metabolic Regulation: Preclinical data indicates that continuous Humanin exposure improves systemic insulin action and reduces weight gain in diet-induced obesity models, functioning as a systemic signal for metabolic allostasis.
- Macrophage Modulation: Recent studies highlight that Humanin reduces the accumulation of lipid droplets in macrophages and shifts their polarization away from pro-inflammatory phenotypes, indicating a role in mitigating the progression of atherosclerotic plaques.
Form & Analytical Testing
This material is produced via robust solid-phase chemical synthesis and supplied as a lyophilized (freeze-dried) powder.
- Lyophilization: Removes water content under vacuum to maintain compound integrity and extend shelf-life.
- Identity Verification: Each lot undergoes Mass Spectrometry (MS) to confirm molecular weight and identity.
- Purity Verification: High-Performance Liquid Chromatography (HPLC) is performed to ensure the product meets the ≥99% purity standard required for reproducible research data.
Storage & Handling
Stable at room temperature for up to 90 days. For long-term storage, keep at -20C (-4F) or colder. Once mixed with a solvent (e.g., bacteriostatic water), the solution must be stored at 4C (39F) and utilized within 30 days. Avoid repeated freeze-thaw cycles, as this degrades the delicate peptide structure.
Referenced Citations
References are provided for informational purposes only and are not clinical claims.
- Guo, B., Zhai, D., Cabezas, E., Welsh, K., Nouraini, S., Satterthwait, A. C., & Reed, J. C. (2003). Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature, 423(6938), 456-461. https://doi.org/10.1038/nature01536
- Ying, G., Iribarren, P., Zhou, Y., Gong, W., Zhang, N., Yu, Z. X., … & Wang, J. M. (2004). Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. The Journal of Immunology, 172(11), 7078-7085. https://doi.org/10.4049/jimmunol.172.11.7078
- Bachar, A. R., Scheffer, L., Schroeder, A. S., DeKelver, R. C., Halo, T. L., Ahn, B. S., … & Cohen, P. (2010). Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced apoptosis. Cardiovascular Research, 88(2), 360-366. https://doi.org/10.1093/cvr/cvq235
- Kim, S. J., Xiao, J., Wan, J., Cohen, P., & Yen, K. (2017). Mitochondrially derived peptides as novel regulators of metabolism. The Journal of Physiology, 595(21), 6613-6621. https://doi.org/10.1113/JP274472
- Zaręba-Kozioł, M., Bartkowiak-Maciejewska, A., & Wójtowicz, T. (2021). Mitochondrial-Derived Peptides in Neurodegenerative Diseases. International Journal of Molecular Sciences, 22(19), 10712. https://doi.org/10.3390/ijms221910712
RESEARCH USE ONLY
This product is intended strictly for laboratory research use only. It is not for human or veterinary use. It is not intended for diagnosis, treatment, cure, or prevention of any disease. All purchases are subject to our Terms of Service and Purity Guarantee.
No COAs available for this product.
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