Sirtuin 6 Protects Against Oxidative Stress and Vascular Dysfunction in Mice.
Sirtuin 6 Protects Against Oxidative Stress and Vascular Dysfunction in Mice.
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DOI：
10.3389/fphys.2021.753501
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发表时间：
2021
影响因子：
4
通讯作者：
Miller JD
中科院分区：
文献类型：
--
作者：
Greiten LE;Zhang B;Roos CM;Hagler M;Jahns FP;Miller JD
目的：沉默调节蛋白脱乙酰酶是生物体衰老的主要调节因子，而小鼠中沉默调节蛋白6（SIRT 6）的缺失导致了深刻的早衰症表型，SIRT 6在调节血管功能中的作用尚不清楚。因此，我们的目的是检验SIRT 6减少引起年轻的遗传改变小鼠内皮功能障碍的假设。结果和方法：我们使用年轻（3个月大），同窝匹配，SIRT 6野生型（WT），和SIRT 6杂合子（HET）小鼠。SIRT 6表达（qRT-PCR）在HET小鼠中减少50%。颈动脉血管反应乙酰胆碱，硝普钠，U46619，和5-羟色胺进行了检查，在离体器官室浴。与同窝匹配的WT对照组相比，HET小鼠对乙酰胆碱（ACH）的舒张反应受损（分别为67 ± 3%和76 ± 3%; p < 0.05），而对硝普钠的反应无变化。在HET小鼠的血管中，用NAD（P）H氧化酶抑制剂夹竹桃苷短期孵育颈动脉环显著改善，但在WT同窝小鼠中则没有。与WT同窝小鼠相比，HET小鼠对U46619或5-羟色胺产生的峰值张力显著减弱。结论：SIRT 6是管道血管扩张功能的关键调节因子。更具体地说，我们提出SIRT 6作为NAD（P）H氧化酶表达和激活的紧张性抑制剂，因为NAD（P）H氧化酶的抑制改善了SIRT 6单倍不足小鼠的内皮功能。总的来说，SIRT 6激活和/或组蛋白乙酰转移酶抑制可能是减少内皮功能障碍和对抗年龄相关性心血管疾病的有用治疗方法。
Objective: Sirtuin deacetylases are major regulators of organismal aging, and while depletion of sirtuin 6 (SIRT6) in mice results in a profound progeroid phenotype, the role of SIRT6 in the regulation of vasomotor function is unknown. Thus, our objective was to test the hypothesis that reductions in SIRT6 elicit endothelial dysfunction in young, genetically altered mice. Results and Approach: We used young (3 month old), littermate-matched, SIRT6 wild-type (WT), and SIRT6 heterozygous (HET) mice. SIRT6 expression (qRT-PCR) was reduced by 50% in HET mice. Carotid vessel responses to acetylcholine, sodium nitroprusside, U46619, and serotonin were examined in isolated organ chamber baths. Relaxation in response to acetylcholine (ACH) was impaired in HET mice compared to littermate-matched WT controls (67 ± 3% versus 76 ± 3%, respectively; p < 0.05), while responses to sodium nitroprusside were unchanged. Short-term incubation of carotid rings with the NAD(P)H oxidase inhibitor, apocynin, significantly improved in vessels from HET mice but not their WT littermates. Peak tension generated in response to either U46619 or serotonin was significantly blunted in HET mice compared to their WT littermates. Conclusion: These data suggest that SIRT6 is a key regulator of vasomotor function in conduit vessels. More specifically, we propose that SIRT6 serves as a tonic suppressor of NAD(P)H oxidase expression and activation, as inhibition of NAD(P)H oxidase improved endothelial function in SIRT6 haploinsufficient mice. Collectively, SIRT6 activation and/or histone acetyltransferase inhibition may be useful therapeutic approaches to reduce endothelial dysfunction and combat age-associated cardiovascular disease.
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DOI：
10.18632/aging.101068
发表时间：
2016-10-15
期刊：
Aging
影响因子：
--
作者：
Kitada M;Ogura Y;Koya D
通讯作者：
Koya D
Sirt6 在肥胖和糖尿病中的作用。
影响因子：
4
作者：
Kuang J;Chen L;Tang Q;Zhang J;Li Y;He J
通讯作者：
He J
影响因子：
20.1
作者：
Grootaert MOJ;Finigan A;Figg NL;Uryga AK;Bennett MR
通讯作者：
Bennett MR
DOI：
10.1253/circj.cj-08-1082
发表时间：
2009-02
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
--
作者：
Heistad DD;Wakisaka Y;Miller J;Chu Y;Pena-Silva R
通讯作者：
Pena-Silva R
影响因子：
10.8
作者：
Hagler, Michael A.;Hadley, Thomas M.;Miller, Jordan D.
通讯作者：
Miller, Jordan D.