title: Sulfide induces apoptosis and Rho kinase-dependent cell blebbing in Jurkat cells.
abstract: Hydrogen sulfide (H₂S) is a toxic gaseous substance, and accidental exposure to high concentrations of H₂S has been reported to be lethal to humans. Inhaled and absorbed H₂S is partially dissolved within the circulation and causes toxic effects on lymphocytes. However, the mechanisms involved in H₂S toxicity have not been well documented. In this study, we examined the cellular uptake and injury of sulfide-exposed human T lymphocytes (Jurkat). Cells were exposed to a H₂S donor, sodium hydroxysulfide (NaHS), at pH 6.0, 7.0, or 8.0 for 1 h at 37 °C in a sealed conical tube to avoid the loss of dissolved H₂S gas. Cytotoxicity and cellular sulfide concentrations increased dramatically as the pH of the NaHS solution decreased. Sulfide enhanced the cleavage of caspase-3 and poly (ADP-ribose) polymerase and induced early cellular apoptosis. A pan-caspase inhibitor reduced sulfide-induced apoptosis. These results indicate that sulfide induces pH-dependent and caspase-dependent apoptosis. We also found that blebbing of the plasma membrane occurred in sulfide-exposed cells. Both ROCK-1 and ROCK-2 (Rho kinases) were activated by sulfide, and sulfide-induced cell blebbing was suppressed by a ROCK inhibitor, suggesting that a Rho pathway is involved in sulfide-induced blebbing in lymphocytes.
authors.affiliation: Department of Legal Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan. sanae@marianna-u.ac.jp
authors.forename: Sanae
authors.initials: S
authors.lastname: Kanno
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Morihisa
authors.initials: M
authors.lastname: Sagi
authors.forename: Shoetsu
authors.initials: S
authors.lastname: Chiba
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshita
authors.forename: Toru
authors.initials: T
authors.lastname: Ikawa
authors.forename: Kazue
authors.initials: K
authors.lastname: Ichiba
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nagai
authors.forename: Meri
authors.initials: M
authors.lastname: Takada
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Toshiji
authors.initials: T
authors.lastname: Mukai
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000633:toxicity*; D006863:Hydrogen-Ion Concentration; D019169:Jurkat Cells; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000378:metabolism / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; D047428:Protein Kinase Inhibitors; D013440:Sulfides; D011065:Poly(ADP-ribose) Polymerases; C515851:ROCK1 protein, human; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; C025451:sodium bisulfide; D006862:Hydrogen Sulfide