PARP-1 inhibition does not restore oxidant-mediated reduction in SIRT1 activity.
PARP-1 inhibition does not restore oxidant-mediated reduction in SIRT1 activity.
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DOI：
10.1016/j.bbrc.2009.12.161
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发表时间：
2010-02-12
影响因子：
3.1
通讯作者：
Rahman, Irfan
中科院分区：
文献类型：
--
作者：
Caito, Samuel;Hwang, Jae-woong;Chung, Sangwoon;Yao, Hongwei;Sundar, Isaac K.;Rahman, Irfan
Sirtuin 1（SIRT 1）脱乙酰酶和聚（ADP-核糖）-聚合酶-1（PARP-1）响应于环境线索，并且两者都需要NAD+辅因子来进行其酶活性。然而，环境/氧化应激介导的PARP-1和SIRT 1通过NAD+辅因子的可用性激活之间的功能联系尚不清楚。我们研究了PARP-1激活引起的NAD+耗竭是否在环境刺激/氧化剂诱导的SIRT 1活性降低中起作用。H2 O2和香烟烟雾（CS）降低细胞内NAD+水平在体外肺上皮细胞和在体内暴露于CS的小鼠肺。药理学PARP-1抑制可防止氧化剂诱导的NAD+损失并减弱SIRT 1活性损失。氧化剂降低了肺上皮细胞中的SIRT 1活性;然而，通过PARP-1抑制或NAD+前体增加细胞NAD+辅因子水平无法恢复SIRT 1活性。发现SIRT 1被CS羰基化，这不能被PARP-1抑制剂或选择性SIRT 1激活剂逆转。总体而言，这些数据表明，环境/氧化应激诱导的SIRT 1下调和PARP-1激活是独立的事件，尽管这两种酶共享相同的辅因子。
Sirtuin1 (SIRT1) deacetylase and poly(ADP-ribose)-polymerase-1 (PARP-1) respond to environmental cues, and both require NAD+ cofactor for their enzymatic activities. However, the functional link between environmental/oxidative stress-mediated activation of PARP-1 and SIRT1 through NAD+ cofactor availability is not known. We investigated whether NAD+ depletion by PARP-1 activation plays a role in environmental stimuli/oxidant-induced reduction in SIRT1 activity. Both H2O2 and cigarette smoke (CS) decreased intracellular NAD+ levels in vitro in lung epithelial cells and in vivo in lungs of mice exposed to CS. Pharmacological PARP-1 inhibition prevented oxidant-induced NAD+ loss and attenuated loss of SIRT1 activity. Oxidants decreased SIRT1 activity in lung epithelial cells; however increasing cellular NAD+ cofactor levels by PARP-1 inhibition or NAD+ precursors was unable to restore SIRT1 activity. SIRT1 was found to be carbonylated by CS, which was not reversed by PARP-1 inhibition or selective SIRT1 activator. Overall, these data suggest that environmental/oxidant stress-induced SIRT1 down-regulation and PARP-1 activation are independent events despite both enzymes sharing the same cofactor.
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影响因子：
25.7
作者：
Yuan H;Shyy JY;Martins-Green M
通讯作者：
Martins-Green M
影响因子：
3.5
作者：
Ho, Cynthia;van der Veer, Eric;Pickering, J. Geoffrey
通讯作者：
Pickering, J. Geoffrey
DOI：
10.1152/ajplung.00439.2007
发表时间：
2008-06-01
影响因子：
4.9
作者：
Yao, Hongwei;Edirisinghe, Indika;Rahman, Irfan
通讯作者：
Rahman, Irfan
影响因子：
4.8
作者：
Hassa, PO;Buerki, C;Hottiger, MO
通讯作者：
Hottiger, MO
影响因子：
2.6
作者：
Kamp, DW;Srinivasan, M;Weitzman, SA
通讯作者：
Weitzman, SA