Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice

Yinrui MA; Zhaohui HE

doi:10.16016/j.2097-0927.202401084

您当前的位置：

首页 >

文章列表页 >

Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice

Basic Medicine | 更新时间：2026-01-09

- Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice
- Journal of Army Medical University Vol. 46, Issue 17, Pages: 1976-1984(2024)
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院神经外科
- 作者简介：
- 基金信息：
  
  the General Program of National Nature Foundation of China(81870927);the Natural Science Foundation Project of Chongqing Science and Technology Commission(CSTB2023NSCQ-MSX0112)
- DOI：10.16016/j.2097-0927.202401084
  CLC： R345;R363.21;R743.35
- Received：21 January 2024，
  
  Revised：2024-03-24，
  
  Published：15 September 2024
- 稿件说明：
移动端阅览
Yinrui MA, Zhaohui HE. Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice[J]. Journal of Army Medical University, 2024, 46(17): 1976-1984.
DOI：

Yinrui MA, Zhaohui HE. Senp1 mediates neuronal pyroptosis after subarachnoid hemorrhage in mice[J]. Journal of Army Medical University, 2024, 46(17): 1976-1984. DOI： 10.16016/j.2097-0927.202401084.

摘要

目的

探究SUMO特异性蛋白酶1(SUMO-specific protease 1，Senp1)在蛛网膜下腔出血(subarachnoid hemorrhage，SAH)中参与神经元焦亡的机制。

方法

95只6~8周龄雄性C57BL/6小鼠采用随机数字表法分为假手术(sham)组(

=15)、SAH(6、12、24、48、72 h)组(

=8、7、17、6、6)、SAH+AAV9-NC组(

=19)、SAH+AAV9-sh-Senp1组(

=17)，左侧颈内动脉血管内穿刺建立SAH动物模型，神经行为学评分评价神经功能，HE染色、FJC染色观察脑皮质神经元损伤情况，RT-PCR检测敲低Senp1的mRNA水平，Western blot检测各组Senp1、NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3

NLRP3)、焦孔素D(gasdermin D，GSDMD)、含PYD和CARD域蛋白(PYD and CARD domain containing，ASC)及半胱氨酸蛋白酶-1(Caspase-1)的表达，免疫荧光观察Senp1和NLRP3的定位表达。

结果

SAH后Senp1表达升高，于24 h达到峰值，并表达于脑皮质神经元。与sh

am组相比，SAH组Senp1、NLRP3、GSDMD、ASC和Caspase-1的表达明显升高(

0.01)，神经损伤加重，并且有神经功能障碍；与SAH+AAV9-NC组相比，给予AAV9-sh-Senp1后神经损伤及功能明显改善，Senp1及上述焦亡蛋白NLRP3、GSDMD、ASC、Caspase-1表达明显降低(

0.01)，抑制了NLRP3介导的神经元焦亡。

结论

Senp1在SAH后促进细胞焦亡的发生，介导神经元损伤。

Abstract

Objective

To investigate the mechanism of SUMO-specific protease 1 (Senp1) involved in neuronal pyroptosis in subarachnoid hemorrhage (SAH).

Methods

A total of 95 male C57BL/6 mice (6~8 weeks old) were randomly divided into sham group (

=15)

SAH groups (for 6

48 and 72 h

respectively

6 and 6)

SAH+AAV9-NC group (

=19)

and SAH+AAV9-sh-Senp1 group (

=17). Mouse model of SAH was established by intravascular puncture in the left internal carotid artery. Neurobehavioral scoring was used to evaluate neurological function

HE staining and FJC staining were employed to observe brain injury

RT-PCR was conducted to detect the knockdown of Senp1

Western blotting was applied to measure the expression of Senp1

NOD-like receptor thermal protein domain associated protein 3 (NLRP3)

gasdermin D (GSDMD)

PYD and CARD domain containing (ASC) and Caspase-1

and immunofluorescence assay was performed to observe the locations of Senp1 and NLRP3.

Results

SAH caused the elevated expression of Senp1

which reached a peak in 24 h and located in the cortical neurons. Compared with the sham group

the expression of Senp1

NLRP3

GSDMD

ASC and Caspase-1 were significantly enhanced in the SAH groups (

0.01)

with aggravation of nerve injury and neurological deficits. Administration of AAV9-sh-Senp1 resulted in significantly improved nerve injury and function

decreased expression of above proteins (

0.01)

and inhibited neuron pyroptosis when compared

with the SAH+AAV9-NC group.

Conclusion

Senp1 promotes the occurrence of neuronal pyroptosis and mediates neuronal injury after SAH.

关键词

Keywords

references

CLAASSEN J, PARK S. Spontaneous subarachnoid haemorrhage[J]. Lancet, 2022, 400(10355): 846-862. DOI: 10.1016/S0140-6736(22)00938-2.

NEIFERT S N, CHAPMAN E K, MARTINI M L, et al . Aneurysmal subarachnoid hemorrhage: the last decade[J ] . Transl Stroke Res, 2021, 12(3): 428-446. DOI: 10.1007/s12975-020-00867-0.

ETMINAN N. Aneurysmal subarachnoid hemorrhage: status quo and perspective[J]. Transl Stroke Res, 2015, 6(3): 167-170. DOI: 10.1007/s12975-015-0398-6.

YU P, ZHANG X, LIU N, et al . Pyroptosis: mechanisms and diseases[J ] . Signal Transduct Target Ther, 2021, 6(1): 128. DOI: 10.1038/s41392-021-00507-5.

KOVACS S B, MIAO E A. Gasdermins: effectors of pyroptosis[J]. Trends Cell Biol, 2017, 27(9): 673-684. DOI: 10.1016/j.tcb.2017.05.005.

COLL R C, SCHRODER K, PELEGRÍN P. NLRP3 and pyroptosis blockers for treating inflammatory diseases[J]. Trends Pharmacol Sci, 2022, 43(8): 653-668. DOI: 10.1016/j.tips.2022.04.003.

XU P F, TAO C R, ZHU Y Y, et al . TAK1 mediates neuronal pyroptosis in early brain injury after subarachnoid hemorrhage[J ] . J Neuroinflammation, 2021, 18(1): 188. DOI: 10.1186/s12974-021-02226-8.

XU P F, HONG Y, XIE Y, et al . TREM-1 exacerbates neuroinflammatory injury via NLRP3 inflammasome-mediated pyroptosis in experimental subarachnoid hemorrhage[J ] . Transl Stroke Res, 2021, 12(4): 643-659. DOI: 10.1007/s12975-020-00840-x..

XIA D Y, YUAN J L, JIANG X C, et al . SIRT1 promotes M2 microglia polarization via reducing ROS-mediated NLRP3 inflammasome signaling after subarachnoid hemorrhage[J ] . Front Immunol, 2021, 12: 770744. DOI: 10.3389/fimmu.2021.770744..

YANG D, FA N D, GUO Z, et al . SENP1 protects against pressure overload-induced cardiac remodeling and dysfunction via inhibiting STAT3 signaling[J ] . J Am Heart Assoc, 2022, 11(22): e027004. DOI: 10.1161/JAHA.122.027004..

SAHIN U, DE THÉ H, LALLEMAND-BREITENBACH V. Sumoylation in physiology, pathology and therapy[J]. Cells, 2022, 11(5): 814. DOI: 10.3390/cells11050814.

CAI H, BIAN X Y, CHEN L Y, et al . Selective intra-arterial brain cooling induces cerebral protection against ischemia/reperfusion injury through SENP1-Sirt3 signaling[J ] . Free Radic Biol Med, 2021, 171: 272-283. DOI: 10.1016/j.freeradbiomed.2021.05.026.

GU J M, FAN Y Q, LIU X B, et al . SENP1 protects against myocardial ischaemia/reperfusion injury via a HIF1α-dependent pathway[J ] . Cardiovasc Res, 2014, 104(1): 83-92. DOI: 10.1093/cvr/cvu177..

BARRY R, JOHN S W, LICCARDI G, et al . SUMO-mediated regulation of NLRP3 modulates inflammasome activity[J ] . Nat Commun, 2018, 9(1): 3001. DOI: 10.1038/s41467-018-05321-2.

MO J, ENKHJARGAL B, TRAVIS Z D, et al . AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP-2 pathway after subarachnoid hemorrhage in rats[J ] . Redox Biol, 2019, 20: 75-86. DOI: 10.1016/j.redox.2018.09.022..

FU W Q, CHE X D, TAN J H, et al . Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage[J ] . CNS Neurosci Ther, 2024, 30(3): e14452. DOI: 10.1111/cns.14452.

XIN Y J, CHEN J, ZHANG H X, et al . Dexras1 induces dysdifferentiation of oligodendrocytes and myelin injury by inhibiting the cAMP-CREB pathway after subarachnoid hemorrhage[J ] . Cells, 2022, 11(19): 2976. DOI: 10.3390/cells11192976.

RASS V, HELBOK R. Early brain injury after poor-grade subarachnoid hemorrhage[J]. Curr Neurol Neurosci Rep, 2019, 19(10): 78. DOI: 10.1007/s11910-019-0990-3.

LAUZIER D C, JAYARAMAN K, YUAN J Y, et al . Early brain injury after subarachnoid hemorrhage: incidence and mechanisms[J ] . Stroke, 2023, 54(5): 1426-1440. DOI: 10.1161/STROKEAHA.122.040072.

CHEN J H, LI M C, LIU Z H, et al . Molecular mechanisms of neuronal death in brain injury after subarachnoid hemorrhage[J ] . Front Cell Neurosci, 2022, 16: 1025708. DOI: 10.3389/fncel.2022.1025708.

YUAN B, ZHOU X M, YOU Z Q, et al . Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage[J ] . Cell Death Dis, 2020, 11(1): 76. DOI: 10.1038/s41419-020-2248-z.

LOVELESS R, BLOOMQUIST R, TENG Y. Pyroptosis at the forefront of anticancer immunity[J]. J Exp Clin Cancer Res, 2021, 40(1): 264. DOI: 10.1186/s13046-021-02065-8.

HU X L, CHEN H W, XU H, et al . Role of pyroptosis in traumatic brain and spinal cord injuries[J ] . Int J Biol Sci, 2020, 16(12): 2042-2050. DOI: 10.7150/ijbs.45467.

MOONEN S, KOPER M J, VAN SCHOOR E, et al . Pyroptosis in Alzheimer's disease: cell type-specific activation in microglia, astrocytes and neurons[J ] . Acta Neuropathol, 2023, 145(2): 175-195. DOI: 10.1007/s00401-022-02528-y.

ZHANG H J, WANG Y, ZHU A X, et al . SUMO-specific protease 1 protects neurons from apoptotic death during transient brain ischemia/reperfusion[J ] . Cell Death Dis, 2016, 7(11): e2484. DOI: 10.1038/cddis.2016.290.

CIMAROSTI H, ASHIKAGA E, JAAFARI N, et al . Enhanced SUMOylation and SENP-1 protein levels following oxygen and glucose deprivation in neurones[J ] . J Cereb Blood Flow Metab, 2012, 32(1): 17-22. DOI: 10.1038/jcbfm.2011.146.

SHAO L Y, LIU Y, WANG W B, et al . SUMO1 SUMOylates and SENP3 deSUMOylates NLRP3 to orchestrate the inflammasome activation[J ] . FASEB J, 2020, 34(1): 1497-1515. DOI: 10.1096/fj.201901653R.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Early identification of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage: development and validation of a multifactorial clinical prediction model

Neferine attenuates parkinson’s disease via modulating microglial pyroptosis mediated by ROS/NLRP3/Caspase-1 signaling pathway

Screening and validation of key molecular targets for dihydromyricetin in ameliorating diabetic nephropathy

Autophagy inducer spermidine improves brain injury after intracerebral hemorrhage

Related Author

HE Zhaohui

MA Yinrui

ZHENG Hui

TAO Yihao

JI Xiang

MA Ying

LIU Fenfen

FENG Dan

Related Institution

Department of neurosurgery， the First Affiliated Hospital of Chongqing Medical University

Department of Neurosurgery， the Second Affiliated Hospital of Chongqing Medical University

Department of General Practice， Guizhou Provincial People’s Hospital

Graduate School， Zunyi Medical University

Department of Critical Care Medicine， the First People’s Hospital of Qingzhen City

⁰