ArticleJournal of neurochemistry2012
Cathepsin H functions as an aminopeptidase in secretory vesicles for production of enkephalin and galanin peptide neurotransmitters.
Article in Journal of neurochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Cathepsin Family Proteases in Prodrug Design: Recent Advances.ChemMedChem · 2026Review
- Profiling Endogenous Opioid Peptide Release from Adrenal Chromaffin Cells.ACS chemical neuroscience · 2026Article
- Cathepsins in cellular entry of human pathogenic viruses.Journal of virology · 2025Review
- A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System.Biomedicines · 2025Review
- IGF2BP2 contributes to thyroid cancer progression by enhancing the stability of m6A-modified CTSH mRNA.PloS one · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Enkephalins and Pain Modulation: Mechanisms of Action and Therapeutic Perspectives.Biomolecules · 2024Review
- Genetic insights into serum cathepsins as diagnostic and therapeutic targets in knee and hip osteoarthritis.Scientific reports · 2024Article
- Cathepsin H Knockdown Reverses Radioresistance of Hepatocellular Carcinoma via Metabolic Switch Followed by Apoptosis.International journal of molecular sciences · 2023Article
- Cathepsins in oral diseases: mechanisms and therapeutic implications.Frontiers in immunology · 2023Review
- Breast density and estradiol are associated with distinct different expression patterns of metabolic proteins in normal human breast tissueFrontiers in oncology · 2023Article
- Distinct Dibasic Cleavage Specificities of Neuropeptide-Producing Cathepsin L and Cathepsin V Cysteine Proteases Compared to PC1/3 and PC2 Serine Proteases.ACS chemical neuroscience · 2022Article
- New Insights into the Role of Cysteine Cathepsins in Neuroinflammation.Biomolecules · 2021Review
- Article
- Identifying Receptors for Neuropeptides and Peptide Hormones: Challenges and Recent Progress.ACS chemical biology · 2021Review
- Pulmonary Aptamer Signatures in Children's Interstitial and Diffuse Lung Disease.American journal of respiratory and critical care medicine · 2019Article
- Article
- Diversity of Neuropeptide Cell-Cell Signaling Molecules Generated by Proteolytic Processing Revealed by Neuropeptidomics Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2018Review
- Sequence comparison, molecular modeling, and network analysis predict structural diversity in cysteine proteases from the Cape sundew, Drosera capensis.Computational and structural biotechnology journal · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Peptide neurotransmitters function as key intercellular signaling molecules in the nervous system. These peptides are generated in secretory vesicles from proneuropeptides by proteolytic processing at dibasic residues, followed by removal of N- and/or C-terminal basic residues to form active peptides. Enkephalin biosynthesis from proenkephalin utilizes the cysteine protease cathepsin L and the subtilisin-like prohormone convertase 2 (PC2). Cathepsin L generates peptide intermediates with N-terminal basic residue extensions, which must be removed by an aminopeptidase. In this study, we identified cathepsin H as an aminopeptidase in secretory vesicles that produces (Met)enkephalin (ME) by sequential removal of basic residues from KR-ME and KK-ME, supported by in vivo knockout of the cathepsin H gene. Localization of cathepsin H in secretory vesicles was demonstrated by immunoelectron microscopy and immunofluorescence deconvolution microscopy. Purified human cathepsin H sequentially removes N-terminal basic residues to generate ME, with peptide products characterized by nano-LC-MS/MS tandem mass spectrometry. Cathepsin H shows highest activities for cleaving N-terminal basic residues (Arg and Lys) among amino acid fluorogenic substrates. Notably, knockout of the cathepsin H gene results in reduction of ME in mouse brain. Cathepsin H deficient mice also show a substantial decrease in galanin peptide neurotransmitter levels in brain. These results illustrate a role for cathepsin H as an aminopeptidase for enkephalin and galanin peptide neurotransmitter production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.