ArticlePloS one2011
Mitochondrial dysfunction links ceramide activated HRK expression and cell death.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Molecular pathways, tissue-specific roles, and therapeutic opportunities in mitochondrial resilience-based strategies for insulin resistance.Frontiers in clinical diabetes and healthcare · 2026Review
- Metabolomics for identifying pathways involved in vesicating agent lewisite-induced corneal injury.Experimental eye research · 2023Article
- Mitochondrial gene expression signature predicts prognosis of pediatric acute myeloid leukemia patients.Frontiers in oncology · 2023Article
- Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy.Cells · 2021Article
- JNK Signaling as a Key Modulator of Soft Connective Tissue Physiology, Pathology, and Healing.International journal of molecular sciences · 2020Review
- Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxo-dodecanoyl)-L-homoserine lactone triggers mitochondrial dysfunction and apoptosis in neutrophils through calcium signaling.Medical microbiology and immunology · 2019Article
- Sphingolipids as Emerging Mediators in Retina Degeneration.Frontiers in cellular neuroscience · 2019Review
- Nitrogen mustard-induced corneal injury involves the sphingomyelin-ceramide pathway.The ocular surface · 2018Article
- Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells.Oncotarget · 2017Article
- Examining impacts of ceranib-2 on the proliferation, morphology and ultrastructure of human breast cancer cells.Cytotechnology · 2016Article
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- Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.PloS one · 2016Article
- Mam33 promotes cytochrome c oxidase subunit I translation in Saccharomyces cerevisiae mitochondria.Molecular biology of the cell · 2015Article
- The plant decapeptide OSIP108 prevents copper-induced apoptosis in yeast and human cells.Biochimica et biophysica acta · 2014Article
- Article
- Bioactive lipids-based pH sensitive micelles for co-delivery of doxorubicin and ceramide to overcome multidrug resistance in leukemia.Pharmaceutical research · 2013Article
- JNK1/2 regulates ER-mitochondrial Ca2+ cross-talk during IL-1β-mediated cell death in RINm5F and human primary β-cells.Molecular biology of the cell · 2013Article
- p53 and Ceramide as Collaborators in the Stress Response.International journal of molecular sciences · 2013Article
- Multifunctional protein APPL2 contributes to survival of human glioma cells.Molecular oncology · 2013Article
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeCell death is an essential process in normal development and homeostasis. In eyes, corneal epithelial injury leads to the death of cells in underlying stroma, an event believed to initiate corneal wound healing. The molecular basis of wound induced corneal stromal cell death is not understood in detail. Studies of others have indicated that ceramide may play significant role in stromal cell death following LASIK surgery. We have undertaken the present study to investigate the mechanism of death induced by C6 ceramide in cultures of human corneal stromal (HCSF) fibroblasts.
methodsCultures of HCSF were established from freshly excised corneas. Cell death was induced in low passage (p<4) cultures of HCSF by treating the cells with C6 ceramide or C6 dihydroceramide as a control. Cell death was assessed by Live/Dead cell staining with calcein AM and ethidium homodimer-1 as well as Annexin V staining, caspase activation and TUNEL staining Mitochondrial dysfunction was assessed by Mito Sox Red, JC-1 and cytochrome C release Gene expression was examined by qPCR and western blotting.
resultsOur data demonstrate ceramide caused mitochondrial dysfunction as evident from reduced MTT staining, cyto c release from mitochondria, enhanced generation of ROS, and loss in mitochondrial membrane potential (ΔΨm). Cell death was evident from Live -Dead Cell staining and the inability to reestablish cultures from detached cells. Ceramide induced the expression of the harikari gene(HRK) and up-regulated JNK phosphorylation. In ceramide treated cells HRK was translocated to mitochondria, where it was found to interact with mitochondrial protein p32. The data also demonstrated HRK, p32 and BAD interaction. Ceramide-induced expression of HRK, mitochondrial dysfunction and cell death were reduced by HRK knockdown with HRK siRNA.
conclusionOur data document that ceramide is capable of inducing death of corneal stromal fibroblasts through the induction of HRK mediated mitochondria dysfunction.
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