ArticleFree radical biology & medicine2008
Proline modulates the intracellular redox environment and protects mammalian cells against oxidative stress.
Article in Free radical biology & medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
193 citing papers in PubMed, 381 citations in OpenAlex.
- Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions.Hypertension (Dallas, Tex. : 1979) · 2023Trial
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- Dose-Dependent Effects of Minocycline on Facial Nerve Regeneration: A Microscopic and Molecular Study.Aesthetic plastic surgery · 2026Article
- An animal-derived protein hydrolysate alleviates osmotic stress-induced oxidative damage in tomato by activating ascorbate and glutathione cycle.BMC plant biology · 2026Article
- Compatible Solute Variation and Stress Adaptation in Native Qatari Plants: Focus on Proline.Life (Basel, Switzerland) · 2026Review
- Multi-omics analysis of glutamine and fish collagen peptides in alleviating post-antibioticExperimental and therapeutic medicine · 2026Article
- Gene therapy rescues cone function inMolecular therapy. Advances · 2026Article
- Untargeted Metabolomics of Human Airway Epithelium Reveals Neuroactive Signatures Linked to Pulmonary Neuroendocrine Cell Enrichment and Allergen Exposure.Metabolites · 2026Article
- Polylactic Acid Constructs Induce Metabolic and Proteomic Changes in the Secretome of Adipose-derived MSCs.Stem cell reviews and reports · 2026Article
- The Multifaceted Functions of Plant Asparagine Synthetase: Regulatory Mechanisms and Functional Diversity in Growth and Defense.Plants (Basel, Switzerland) · 2026Review
- Multicellular Model Reveals the Mechanism of AEE Alleviating Vascular Endothelial Cell Injury via Anti-Inflammatory and Antioxidant Effects.International journal of molecular sciences · 2026Article
- Metabolomic profiling reveals alterations in Candida pathophysiology and host interactions during primary oral candidiasis and following antifungal treatment.Scientific reports · 2026Article
- Cocoa by-products extracts suppress viral replication and oxidative stress in chikungunya virus-infected cells.PloS one · 2026Article
- Nutrient assessment of sea buckthorn residues as potential feed ingredients.Frontiers in veterinary science · 2026Article
- Metabolic reprogramming induced by CRP deficiency or human CRP transgenic in influenza-infected mice.Frontiers in immunology · 2026Article
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- AMPK agonism optimizes the in vivo activation and antileukemic efficacy of chimeric antigen receptor T cells.Journal for immunotherapy of cancer · 2025Article
- Comparative Metabolomic Approaches to Nanoplastic Toxicity in Mammalian and Aquatic Systems.International journal of molecular sciences · 2025Review
- Effects of proline on growth performance, protein synthesis and cold resistance in white shrimp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Beyond Protein Building Blocks: A Review of Biological Roles and Therapeutic Potential of Free Amino Acids.International journal of molecular sciences · 2025Review
133 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The potential of proline to suppress reactive oxygen species (ROS) and apoptosis in mammalian cells was tested by manipulating intracellular proline levels exogenously and endogenously by overexpression of proline metabolic enzymes. Proline was observed to protect cells against H(2)O(2), tert-butyl hydroperoxide, and a carcinogenic oxidative stress inducer but was not effective against superoxide generators such as menadione. Oxidative stress protection by proline requires the secondary amine of the pyrrolidine ring and involves preservation of the glutathione redox environment. Overexpression of proline dehydrogenase (PRODH), a mitochondrial flavoenzyme that oxidizes proline, resulted in 6-fold lower intracellular proline content and decreased cell survival relative to control cells. Cells overexpressing PRODH were rescued by pipecolate, an analog that mimics the antioxidant properties of proline, and by tetrahydro-2-furoic acid, a specific inhibitor of PRODH. In contrast, overexpression of the proline biosynthetic enzymes Delta(1)-pyrroline-5-carboxylate (P5C) synthetase (P5CS) and P5C reductase (P5CR) resulted in 2-fold higher proline content, significantly lower ROS levels, and increased cell survival relative to control cells. In different mammalian cell lines exposed to physiological H(2)O(2) levels, increased endogenous P5CS and P5CR expression was observed, indicating that upregulation of proline biosynthesis is an oxidative stress response.
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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.