title: Simulated microgravity increases heavy ion radiation-induced apoptosis in human B lymphoblasts.
abstract: OBJECTIVE
  Microgravity and radiation, common in space, are the main factors influencing astronauts' health in space flight, but their combined effects on immune cells are extremely limited. Therefore, the effect of simulated microgravity on heavy ion radiation-induced apoptosis, and reactive oxygen species (ROS)-sensitive apoptosis signaling were investigated in human B lymphoblast HMy2.CIR cells.
  
  
  METHODS
  Simulated microgravity was achieved using a Rotating Wall Vessel Bioreactor at 37°C for 30 min. Heavy carbon-ion irradiation was carried out at 300 MeV/u, with a linear energy transfer (LET) value of 30 keV/μm and a dose rate of 1Gy/min. Cell survival was evaluated using the Trypan blue exclusion assay. Apoptosis was indicated by Annexin V/propidium iodide staining. ROS production was assessed by cytometry with a fluorescent probe dichlorofluorescein. Malondialdehyde was detected using a kit. Extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase phosphatase-1 (MKP-1) and caspase-3 activation were measured by immunoblotting.
  
  
  RESULTS
  Simulated microgravity decreased heavy ion radiation-induced cell survival and increased apoptosis in HMy2.CIR cells. It also amplified heavy ion radiation-elicited intracellular ROS generation, which induced ROS-sensitive ERK/MKP-1/caspase-3 activation in HMy2.CIR cells. The above phenomena could be reversed by the antioxidants N-acetyl cysteine (NAC) and quercetin.
  
  
  CONCLUSIONS
  These results illustrated that simulated microgravity increased heavy ion radiation-induced cell apoptosis, mediated by a ROS-sensitive signal pathway in human B lymphoblasts. Further, the antioxidants NAC and quercetin, especially NAC, might be good candidate drugs for protecting astronauts' and space travelers' health and safety.
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Bingrong
authors.initials: B
authors.lastname: Dang
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Erdong
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Xiangquan
authors.initials: X
authors.lastname: Mi
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Yan
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Zhuanzi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Institute of Radiology Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.affiliation: School of Life Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address: linc@lzu.edu.cn.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000528:radiation effects*; D001402:B-Lymphocytes / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003359:Cosmic Radiation; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020450:Heavy Ions; D006801:Humans; D018499:Linear Energy Transfer; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000528:radiation effects*; D018474:Weightlessness Simulation
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D011794:Quercetin; D048049:Extracellular Signal-Regulated MAP Kinases; D054638:Dual Specificity Phosphatase 1; D053148:Caspase 3; D000111:Acetylcysteine
keywords: Apoptosis; HMy2.CIR cells; Heavy ion radiation; Reactive oxygen species; Simulated microgravity