Biphasic response of checkpoint control proteins in hyperoxia: exposure to lower levels of oxygen induces genome maintenance genes in experimental baboon BPD.
Biphasic response of checkpoint control proteins in hyperoxia: exposure to lower levels of oxygen induces genome maintenance genes in experimental baboon BPD.
复制标题
检查点控制蛋白在高氧中的双相反应：暴露于较低水平的氧气会诱导实验性狒狒BPD中的基因组维持基因。
DOI：
10.1007/s11010-014-2124-1
复制
发表时间：
2014-10
影响因子：
4.3
通讯作者：
Wasnick JD
中科院分区：
文献类型：
--
作者：
Das KC;Wasnick JD
呼吸高浓度氧气(高氧)会导致肺损伤，并与肺部疾病有关，如支气管肺发育不良(BPD)、呼吸窘迫综合征(RDS)和新生儿持续性肺动脉高压(PPHN)。高氧(95-100%O2)会导致肺细胞DNA损伤和生长停滞，从而导致细胞凋亡或坏死。虽然补充氧疗在临床上很重要，但允许肺细胞重新进入细胞周期的高氧暴露的水平和持续时间仍不清楚。我们假设，暴露在较低浓度高氧下的细胞在室内空气中恢复时，将保持进入细胞周期的能力。我们使用不同浓度的氧气(21-95%)来确定肺细胞对高氧的反应。我们的结果表明，当暴露在超过60%的氧气中时，细胞生长停滞，无法重新进入细胞周期。细胞周期检查点蛋白以两相的方式增加，增加到70%氧气，但在超过90%氧气时下降。基因芯片分析显示，90%氧气暴露48小时后，CDKs6-8和视网膜母细胞瘤蛋白(Rb)、p107和p130的丰度显著降低。我们在早产儿(125d和140d)的支气管肺发育不良(BPD)模型上进一步测试了临床上相关的需要氧[(prorenada，PRN)]的效果。基因芯片结果显示，暴露6天或14天的PRN氧暴露动物已诱导了与抗炎、增殖和分化相关的染色体维持基因(MCM)的表达。
Breathing high concentrations of oxygen (hyperoxia) causes lung injury and is associated with lung diseases such as bronchopulmonary dysplasia (BPD), respiratory distress syndrome (RDS) and persistent pulmonary hypertension of the newborns (PPHN). Hyperoxia (95–100%O2) causes DNA damage and growth arrest of lung cells and consequently cells die by apoptosis or necrosis. Although supplemental oxygen therapy is clinically important, the level and duration of hyperoxic exposure that would allow lung cells to reenter the cell cycle remains unclear. We hypothesized that cells exposed lower concentrations of hyperoxia will retain the capacity to enter cell cycle when recovered in room air. We employed varying concentrations of oxygen (21–95%) to determine the response of lung cells to hyperoxia. Our results indicate that cells were growth arrested and failed to reenter the cell cycle when exposed to greater than 60% oxygen. Cell cycle checkpoint proteins were increased in a biphasic manner, increasing until 70% oxygen, but declined in greater than 90% oxygen. Microarray analysis shows that there is significant decrease in the abundance of Cdks 6–8 and retinoblastoma protein (Rb), p107 and p130 in exposure to 90% oxygen for 48 hours. We further tested the effect of clinically relevant as needed oxygen [(pro-re-nada (prn)] in premature infant (125d and 140d) baboon model of bronchopulmonary dysplasia (BPD). The microarray results show that 6 or 14d PRN oxygen exposed animals had induced expression of chromosomal maintenance genes (MCMs), genes related to anti-inflammation, proliferation and differentiation.
登录
查看更多内容
DOI：
10.1152/ajplung.00203.2002
发表时间：
2004-01-01
影响因子：
4.9
作者：
Das, KC;Dashnamoorthy, R
通讯作者：
Dashnamoorthy, R
DOI：
10.1073/pnas.96.5.2147
发表时间：
1999-03-02
影响因子：
11.1
作者：
Innocente, SA;Abrahamson, JLA;Lee, JM
通讯作者：
Lee, JM
DOI：
10.1152/ajplung.00004.2008
发表时间：
2008-05-01
影响因子：
4.9
作者：
Kulkarni, Amit;Das, Kumuda C.
通讯作者：
Das, Kumuda C.
DOI：
10.1073/pnas.91.25.12248
发表时间：
1994-12-06
影响因子：
11.1
作者：
GARDNER, PR;NGUYEN, DDH;WHITE, CW
通讯作者：
WHITE, CW
影响因子：
6.6
作者：
Das, KC;Ravi, D
通讯作者：
Ravi, D