title: Downregulation of Endogenous Hydrogen Sulfide Pathway Is Involved in Mitochondrion-Related Endothelial Cell Apoptosis Induced by High Salt.
abstract: BACKGROUND
  The study aimed to investigate whether endogenous H2S pathway was involved in high-salt-stimulated mitochondria-related vascular endothelial cell (VEC) apoptosis.
  
  
  METHODS
  Cultured human umbilical vein endothelial cells (HUVECs) were used in the study. H2S content in the supernatant was detected. Western blot was used to detect expression of cystathionine gamma-lyase (CSE), cleaved-caspase-3, and mitochondrial and cytosolic cytochrome c (cytc). Fluorescent probes were used to quantitatively detect superoxide anion generation and measure the in situ superoxide anion generation in HUVEC. Mitochondrial membrane pore opening, mitochondrial membrane potential, and caspase-9 activities were measured. The cell apoptosis was detected by cell death ELISA and TdT-mediated dUTP nick end labeling (TUNEL) methods.
  
  
  RESULTS
  High-salt treatment downregulated the endogenous VEC H2S/CSE pathway, in association with increased generation of oxygen free radicals, decreased mitochondrial membrane potential, enhanced the opening of mitochondrial membrane permeability transition pore and leakage of mitochondrial cytc, activated cytoplasmic caspase-9 and caspase-3 and subsequently induced VEC apoptosis. However, supplementation of H2S donor markedly inhibited VEC oxidative stress and mitochondria-related VEC apoptosis induced by high salt.
  
  
  CONCLUSIONS
  H2S/CSE pathway is an important endogenous defensive system in endothelial cells antagonizing high-salt insult. The protective mechanisms for VEC damage might involve inhibiting oxidative stress and protecting mitochondrial injury.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Siyao
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Qingyou
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China ; Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China ; Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D012492:Salts / Q000633:toxicity*; D013440:Sulfides / Q000494:pharmacology
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D012492:Salts; D013440:Sulfides; D045304:Cytochromes c; D053148:Caspase 3; D053453:Caspase 9; D003542:Cystathionine gamma-Lyase; C033479:sodium sulfide; D006862:Hydrogen Sulfide