Butyric acid induces apoptosis via oxidative stress in Jurkat T-cells.
Reactive oxygen species (ROS) are essential for the induction of T-cell apoptosis by butyric acid, an extracellular metabolite of periodontopathic bacteria. To determine the involvement of oxidative stress in apoptosis pathways, we investigated the contribution of ROS in mitochondrial signaling pathways, death-receptor-initiated signaling pathway, and endoplasmic reticulum stress in butyric-acid-induced T-cell apoptosis. N-acetyl-L-Cysteine (NAC) abrogated mitochondrial injury, cytochrome c, AIF, and Smac release, and Bcl-2 and Bcl-xL suppression and Bax and Bad activation induced by butyric acid. However, the decrease in cFLIP expression by butyric acid was not restored by treatment with NAC; increases in caspase-4 and -10 activities by butyric acid were completely abrogated by NAC. NAC also affected the elevation of GRP78 and CHOP/GADD153 expression by butyric acid. These results suggest that butyric acid is involved in mitochondrial-dysfunction- and endoplasmic reticulum stress-mediated apoptosis in human Jurkat T-cells via a ROS-dependent mechanism.
Kurita-Ochiai
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Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo, Chiba 271-8587, Japan. ochiai.tomoko@nihon-u.ac.jp
Ochiai
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D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D020148:Butyric Acid / Q000494:pharmacology*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000187:drug effects; D053455:Caspase 10 / Q000187:drug effects; D061945:Caspase Inhibitors; D053471:Caspases, Initiator / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D016166:Free Radical Scavengers / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000494:pharmacology; D053218:Receptors, Death Domain / Q000187:drug effects; D015843:Serpins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D014764:Viral Proteins / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000187:drug effects; D051020:bcl-X Protein / Q000187:drug effects
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; C494819:BAD protein, human; C494811:BCL2L1 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C412403:DIABLO protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D016166:Free Radical Scavengers; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D015843:Serpins; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D020148:Butyric Acid; D045304:Cytochromes c; C074641:interleukin-1beta-converting enzyme inhibitor; C093516:CASP4 protein, human; D053455:Caspase 10; D053471:Caspases, Initiator; C506438:CASP10 protein, human; D000111:Acetylcysteine