ArticleFree radical biology & medicine2012
Proline dehydrogenase is essential for proline protection against hydrogen peroxide-induced cell death.
Article in Free radical biology & medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 149 citations in OpenAlex.
- Association between salivary microbiota-related amino acid metabolic dysregulation and tacrolimus-induced gingival overgrowth following kidney transplantation.BMC oral health · 2026Article
- Effects of proline on growth performance, protein synthesis and cold resistance in white shrimp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Serum metabolomics reveals distinctive signature of cancer staging in oral squamous cell carcinoma.BMC oral health · 2025Article
- GmAP2 enhances plant tolerance to aluminum toxicity and phosphorus deficiency in Arabidopsis.Plant cell reports · 2025Article
- Proline Metabolism in Cancer: Emerging Roles in Redox Homeostasis and Therapeutic Opportunities.Cancers · 2025Review
- Amino Acid Restriction Impairs Human Endometrial Stromal Cell Decidualization and Is Rescued by Proline Supplementation.Journal of cellular and molecular medicine · 2025Article
- Article
- Impact of Water Stress on Metabolic Intermediates and Regulators in Broccoli Sprouts, and Cellular Defense Potential of Their Extracts.International journal of molecular sciences · 2025Article
- Article
- Proline metabolism is essential for alkaline adaptation of Nile tilapia (Oreochromis niloticus).Journal of animal science and biotechnology · 2024Article
- Proline metabolic reprogramming modulates cardiac remodeling induced by pressure overload in the heart.Science advances · 2024Article
- Palmitate induces integrated stress response and lipoapoptosis in trophoblasts.Cell death & disease · 2024Article
- Article
- Effects of FeMicrobial cell factories · 2023Article
- Review
- Integrated physiological and transcriptional dissection reveals the core genes involving nutrient transport and osmoregulatory substance biosynthesis in allohexaploid wheat seedlings under salt stress.BMC plant biology · 2022Article
- Dual contribution of the mTOR pathway and of the metabolism of amino acids in prostate cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Beneficial Effect of Proline Supplementation on Goat Spermatozoa Quality during Cryopreservation.Animals : an open access journal from MDPI · 2022Article
- Stress-induced activation of the proline biosynthetic pathway in Bacillus subtilis: a population-wide and single-cell study of the osmotically controlled proHJ promoter.Microbial biotechnology · 2022Article
- Proline confers acid stress tolerance to Bacillus megaterium G18.Scientific reports · 2022Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Proline metabolism has an underlying role in apoptotic signaling that influences tumorigenesis. Proline is oxidized to glutamate in the mitochondria, with the rate-limiting step catalyzed by proline dehydrogenase (PRODH). PRODH expression is inducible by p53, leading to increased proline oxidation, reactive oxygen species formation, and induction of apoptosis. Paradoxical to its role in apoptosis, proline also protects cells against oxidative stress. Here we explore the mechanism of proline protection against hydrogen peroxide stress in melanoma WM35 cells. Treatment of WM35 cells with proline significantly increased cell viability, diminished oxidative damage of cellular lipids and proteins, and maintained ATP and NADPH levels after exposure to hydrogen peroxide. Inhibition or siRNA-mediated knockdown of PRODH abolished proline protection against oxidative stress, whereas knockdown of Δ(1)-pyrroline-5-carboxylate reductase, a key enzyme in proline biosynthesis, had no impact on proline protection. Potential linkages between proline metabolism and signaling pathways were explored. The combined inhibition of the mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 eliminated proline protection. A significant increase in Akt activation was observed in proline-treated cells after hydrogen peroxide stress along with a corresponding increase in the phosphorylation of the forkhead transcription factor class O3a (FoxO3a). The role of PRODH in proline-mediated protection was validated in the prostate carcinoma cell line PC3. Knockdown of PRODH in PC3 cells attenuated phosphorylated levels of Akt and FoxO3a and decreased cell survival during hydrogen peroxide stress. The results provide evidence that PRODH is essential in proline protection against hydrogen peroxide-mediated cell death and that proline/PRODH helps activate Akt in cancer cells.
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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.