Description

Product Description

SHLP-1 (Small Humanin-Like Peptide 1) is a mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA (MT-RNR2) region of mitochondrial DNA. As one of the Humanin-like peptides, SHLP-1 represents a recently identified class of bioactive microproteins that play crucial roles in cellular metabolism, stress resistance, and intercellular signaling.

Originally identified through mitochondrial transcriptome analyses, SHLP-1 belongs to a family of small open reading frame (sORF)-encoded peptides that function as mitochondrial signaling molecules, bridging communication between mitochondria and the rest of the cell. These peptides are involved in regulating energy homeostasis, apoptosis, and age-associated pathologies.

Biological Background

Mitochondria are not merely the “powerhouses” of the cell but also serve as signaling centers that regulate oxidative stress, apoptosis, and inflammatory processes. SHLP-1, along with other MDPs such as Humanin and MOTS-c, mediates mitochondrial-to-nuclear communication (retrograde signaling) that influences metabolic adaptation and survival under stress conditions.

SHLP-1 expression has been observed in multiple tissues, including the liver, skeletal muscle, heart, and brain. Experimental findings suggest that SHLP-1 levels decline with aging, paralleling mitochondrial dysfunction and increased oxidative burden.

Research Relevance

SHLP-1 is an emerging therapeutic target and biomarker in several disease models:

• Diabetes and Metabolic Disorders: SHLP-1 enhances insulin sensitivity and glucose metabolism.

• Neurodegeneration: Exhibits neuroprotective properties in models of Alzheimer’s disease by reducing oxidative stress and β-amyloid toxicity.

• Cardiovascular Health: Improves endothelial function and mitigates atherosclerosis by controlling mitochondrial ROS.

• Oncology: Influences apoptosis and metabolic reprogramming in prostate cancer and other tumors.

Structural and Functional Insights

SHLP-1 is a short peptide of 20–25 amino acids, encoded by a cryptic reading frame within mitochondrial 16S rRNA. Despite its small size, SHLP-1 displays potent bioactivity through receptor-mediated and intracellular pathways. Studies indicate that SHLP-1 interacts with cell-surface receptors and may activate AMPK, PI3K/AKT, and STAT3 pathways, leading to increased mitochondrial biogenesis and stress resilience.

Summary of Benefits

• Promotes mitochondrial health and energy production.

• Reduces reactive oxygen species (ROS) and oxidative damage.

• Enhances insulin responsiveness and glucose uptake.

• Provides cytoprotective effects against apoptotic stimuli.

• Supports cardiovascular and neural function in aging models.

SHLP-1 thus represents a multifunctional mitochondrial messenger peptide with applications across metabolic, neurodegenerative, and oncological research fields.

Product Specifications

Mechanism of Action

SHLP-1 functions as a mitochondrial signaling peptide that modulates cellular energy balance, oxidative stress, and survival through multiple intracellular pathways. Its activity is mediated by both autocrine and endocrine mechanisms, acting as a messenger between mitochondria and the nucleus or other organ systems.

1. Mitochondrial-Nuclear Crosstalk

SHLP-1 serves as a retrograde signaling molecule that communicates mitochondrial status to the nucleus. Under stress conditions (e.g., oxidative damage or nutrient deprivation), SHLP-1 levels increase to activate transcriptional responses that enhance cellular antioxidant capacity and mitochondrial biogenesis. This effect involves activation of AMP-activated protein kinase (AMPK) and PGC-1α, leading to improved mitochondrial turnover and energy efficiency.

2. Regulation of Insulin Sensitivity and Metabolism

SHLP-1 improves glucose metabolism by promoting AKT phosphorylation and increasing GLUT4 translocation to the plasma membrane, thereby enhancing glucose uptake in skeletal muscle and adipose tissue. These metabolic effects are accompanied by reductions in circulating insulin levels and lipid peroxidation.

3. Antioxidant Defense and ROS Modulation

Through the PI3K/AKT–Nrf2 axis, SHLP-1 upregulates antioxidant enzymes such as superoxide dismutase (SOD) and catalase. This reduces mitochondrial ROS accumulation, protecting cells from oxidative stress-induced apoptosis.

4. Neuroprotective Effects

In neuronal models, SHLP-1 inhibits the accumulation of amyloid-β aggregates and prevents mitochondrial fragmentation. By stabilizing mitochondrial membranes, SHLP-1 preserves ATP production and calcium homeostasis, contributing to neuronal survival in Alzheimer’s disease models.

5. Cardiovascular and Endothelial Functions

SHLP-1 enhances endothelial nitric oxide synthase (eNOS) activation and maintains vascular relaxation. It reduces endothelial ROS and inflammation, providing anti-atherogenic effects. These findings suggest potential cardioprotective roles through mitochondrial optimization and redox control.

6. Antitumor and Apoptotic Modulation

SHLP-1 may regulate apoptosis in cancer cells via cytochrome c release control and Bcl-2/Bax modulation. In prostate cancer models, it can shift the balance from pro-survival to pro-apoptotic signaling, suppressing tumor growth and proliferation.

Overall, SHLP-1 acts as a multifunctional mitochondrial hormone-like peptide, orchestrating a balance between metabolism, redox signaling, and cell fate determination.

Side Effects

As a mitochondrial peptide under preclinical research, SHLP-1’s adverse profiles are limited to experimental observations:

• Metabolic Modulation: Overexpression or high concentrations may alter insulin signaling in non-target tissues.

• Mitochondrial Overactivation: Excessive mitochondrial biogenesis could disrupt cellular energy balance.

• ROS Undershoot: Over-suppression of ROS may impair redox-dependent signaling necessary for normal adaptation.

• Immune Effects: In some models, SHLP-1 influences cytokine secretion and may alter immune tolerance.

• Potential Hormonal Cross-talk: As a peptide hormone mimic, it could influence endocrine networks in vivo.

Researchers are advised to use controlled dosages and well-characterized systems when exploring SHLP-1 mechanisms.

Disclaimer

For research use only. Not intended for human or veterinary use, diagnosis, or treatment.

Keywords

SHLP-1, mitochondrial-derived peptide, MT-RNR2, Humanin-like peptide, mitochondrial signaling, AMPK, Nrf2, oxidative stress, insulin sensitivity, diabetes research, neuroprotection, Alzheimer’s disease, mitochondrial biology, cancer metabolism.

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