1.中山大学公共卫生学院,广东 广州 510080
2.中山大学公共卫生学院(深圳),广东 深圳 518106
3.广东省营养膳食与健康重点实验室,广东 广州 510080
4.广东省营养转化工程技术研究中心,广东 广州 510080
5.大理大学公共卫生学院,云南 大理 671003
6.广州市妇女儿童医疗中心,广东 广州 510623
施译琳,硕士生,研究方向:营养与慢性病防治,E-mail: shiylin5@mail2.sysu.edu.cn
收稿:2021-06-02,
纸质出版:2022-01-20
移动端阅览
施译琳,杨奥林,王锐杰等.辅酶Q10抑制过氧化氢诱导的血小板线粒体功能紊乱[J].中山大学学报(医学科学版),2022,43(01):70-76.
SHI Yi-lin,YANG Ao-lin,WANG Rui-jie,et al.Coenzyme Q10 Inhibits Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Platelets[J].Journal of Sun Yat-sen University(Medical Sciences),2022,43(01):70-76.
施译琳,杨奥林,王锐杰等.辅酶Q10抑制过氧化氢诱导的血小板线粒体功能紊乱[J].中山大学学报(医学科学版),2022,43(01):70-76. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0109.
SHI Yi-lin,YANG Ao-lin,WANG Rui-jie,et al.Coenzyme Q10 Inhibits Hydrogen Peroxide-Induced Mitochondrial Dysfunction in Platelets[J].Journal of Sun Yat-sen University(Medical Sciences),2022,43(01):70-76. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2022.0109.
目的
2
探究辅酶Q
10
(CoQ
10
)对过氧化氢(H
2
O
2
)诱导的血小板线粒体功能紊乱的影响并探讨相关机制。
方法
2
采集健康志愿者外周静脉血,制备纯化血小板悬液。用100 μmol/L CoQ
10
与纯化血小板在体外共孵育50 min,再与1 mmol/L H
2
O
2
孵育30 min后(实验重复3次以上),用流式细胞术测定线粒体膜电位、磷脂酰丝氨酸(PS)外翻阳性率、线粒体活性氧簇(mtROS)水平,用酶标仪测定总ROS和ATP浓度,用Western Blot检测血小板p53蛋白磷酸化水平和Bcl-2家族蛋白水平。
结果
2
在静息血小板中,CoQ
10
对线粒体功能无影响(线粒体膜电位、PS外翻阳性率、胞内ROS、mtROS、ATP水平,
P
>
0.05)。在氧化应激模型中,H
2
O
2
使血小板线粒体膜电位下降、PS外翻增加,而CoQ
10
可以显著逆转H
2
O
2
诱导的血小板线粒体膜电位下降[(35.76%±3.94)%
vs
. (21.04%±1.69)%,
P
<
0.05],但对PS外翻无抑制作用(
P
>
0.05)。进一步的机制研究发现,CoQ
10
可以直接抑制H
2
O
2
诱导的胞内ROS、mtROS生成(
P
<
0.05),降低p53磷酸化水平、升高Bcl-2和Bcl-xL表达水平(
P
<
0.05)且不改变ATP含量(
P
>
0.05)。
结论
2
CoQ
10
抑制H
2
O
2
诱导的血小板线粒体功能紊乱,并且抑制p53磷酸化及升高Bcl-2家族抗凋亡蛋白表达。
Objective
2
We explored the protective effects of coenzyme Q
10
(CoQ
10
) on hydrogen peroxide (H
2
O
2
)-induced platelet mitochondrial dysfunction and the underlying mechanisms.
Methods
2
Peripheral venous blood from healthy volunteers was collected to prepare gel-filtered platelet suspension. Gel-filtered platelets were incubated with 100 μmol/L CoQ
10
for 50 min followed by 30 min incubation with H
2
O
2
(
n
≥3 per group). Mitochondrial membrane potential, phosphatidylserine (PS) exposure ratio and mitochondrial reactive oxygen species (mtROS) were measured by flow cytometry. Concentrations of total cellular ROS and ATP were measured by microplate reader. The phosphorylation level of platelet protein p53 and expression levels of Bcl-2 and Bcl-xL were detected by Western blot.
Results
2
In resting platelets, CoQ
10
had no effect on mitochondrial function (mitochondrial membrane potential, PS exposure positive rate, intracellular ROS, mtROS, ATP levels,
P
>
0.05). In the oxidative stress model, H
2
O
2
significantly decreased platelet mitochondrial membrane potential and increase PS exposure in platelets. CoQ
10
significantly inhibited the dissipation of mitochondrial membrane potential induced by H
2
O
2
[(35.76%±3.94)%
vs
. (21.04%±1.69)%,
P
<
0.05], without inhibitory effect on PS exposure (
P
>
0.05). Further mechanism study found that CoQ
10
directly inhibited the production of ROS and mtROS induced by H
2
O
2
(
P
<
0.05), reduced the phosphorylation level of p53 and increased Bcl-2 family expression level (
P
<
0.05) while having no effect on ATP content decrease (
P
>
0.05).
Conclusion
2
CoQ
10
inhibits H
2
O
2
-induced mitochondrial dysfunction in platelets, by reducing p53 phosphorylation and increasing the expression of Bcl-2 family survival protein.
Nording HM , Seizer P , Langer HF . Platelets in inflammation and atherogenesis [J]. Front Immunol , 2015 , 6 : 98 .
Chan DC . Mitochondrial dynamics and its involvement in disease [J]. Annu Rev Pathol , 2020 , 15 : 235 - 259 .
Melchinger H , Jain K , Tyagi T , et al . Role of platelet mitochondria: life in a nucleus-free zone [J]. Front Cardiovasc Med , 2019 , 6 : 153 .
Lee SH , Du J , Stitham J , et al . Inducing mitophagy in diabetic platelets protects against severe oxidative stress [J]. EMBO Mol Med , 2016 , 8 ( 7 ): 779 - 795 .
Sies H . Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress [J]. Redox Biol , 2017 , 11 : 613 - 619 .
McArthur K , Chappaz S , Kile BT . Apoptosis in megakaryocytes and platelets: the life and death of a lineage [J]. Blood , 2018 , 131 ( 6 ): 605 - 610 .
Stefely JA , Pagliarini DJ . Biochemistry of mitochondrial coenzyme Q biosynthesis [J]. Trends Biochem Sci , 2017 , 42 ( 10 ): 824 - 843 .
Yang X , Zhang Y , Xu H , et al . Neuroprotection of coenzyme Q10 in neurodegenerative diseases [J]. Curr Top Med Chem , 2016 , 16 ( 8 ): 858 - 866 .
Choudhury NA , Malyszko J , Ahmed MH , et al . Plasma serotonin and platelet aggregation during ischemia-reperfusion in dogs: effect of dipyridamole and coenzyme Q10 [J]. Haemostasis , 1996 , 26 ( 1 ): 38 - 44 .
Ya F , Xu XR , Shi Y , et al . Coenzyme Q10 upregulates platelet cAMP/PKA pathway and attenuates integrin alphaIIbbeta3 signaling and thrombus growth [J]. Mol Nutr Food Res , 2019 , 63 ( 23 ): e1900662 .
Sies H , Berndt C , Jones DP . Oxidative stress [J]. Annu Rev Biochem , 2017 , 86 : 715 - 748 .
Bhatti JS , Bhatti GK , Reddy PH . Mitochondrial dysfunction and oxidative stress in metabolic disorders - a step towards mitochondria based therapeutic strategies [J]. Biochim Biophys Acta Mol Basis Dis , 2017 , 1863 ( 5 ): 1066 - 1077 .
Aouacheria A , Baghdiguian S , Lamb HM , et al . Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins [J]. Neurochem Int , 2017 , 109 : 141 - 161 .
Thushara RM , Hemshekhar M , Basappa , et al . Biologicals, platelet apoptosis and human diseases: an outlook [J]. Crit Rev Oncol Hematol , 2015 , 93 ( 3 ): 149 - 158 .
Fuentes E , Araya-Maturana R , Urra FA . Regulation of mitochondrial function as a promising target in platelet activation-related diseases [J]. Free Radic Biol Med , 2019 , 136 : 172 - 182 .
Koupenova M , Clancy L , Corkrey HA , et al . Circulating platelets as mediators of immunity, inflammation, and thrombosis [J]. Circ Res , 2018 , 122 ( 2 ): 337 - 351 .
Zhou SF , Yuan J , Liao MY , et al . IL-17A promotes ventricular remodeling after myocardial infarction [J]. J Mol Med (Berl) , 2014 , 92 ( 10 ): 1105 - 1116 .
Su D , Guan L , Gao Q , et al . ROCK1/p53/NOXA signaling mediates cardiomyocyte apoptosis in response to high glucose in vitro and vivo [J]. Biochim Biophys Acta Mol Basis Dis , 2017 , 1863 ( 4 ): 936 - 946 .
Tang WH , Stitham J , Jin Y , et al . Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets [J]. Circulation , 2014 , 129 ( 15 ): 1598 - 1609 .
Lee J , Giordano S , Zhang J. Autophagy , mitochondria and oxidative stress : cross-talk and redox signalling [J]. Biochem J , 2012 , 441 ( 2 ): 523 - 540 .
Chi SW . Structural insights into the transcription-independent apoptotic pathway of p53 [J]. BMB Rep , 2014 , 47 ( 3 ): 167 - 172 .
Amstad PA , Liu H , Ichimiya M , et al . BCL-2 is involved in preventing oxidant-induced cell death and in decreasing oxygen radical production [J]. Redox Rep , 2001 , 6 ( 6 ): 351 - 362 .
Zhang D , Yang B , Chang SQ , et al . Protective effect of paeoniflorin on H2O2 induced Schwann cells injury based on network pharmacology and experimental validation [J]. Chin J Nat Med , 2021 , 19 ( 2 ): 90 - 99 .
Duan P , Hu C , Butler HJ , et al . 4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling [J]. Environ Toxicol , 2017 , 32 ( 3 ): 739 - 753 .
Ziai H , Alenazi A , Hearn M , et al . The association of Bcl-xL and p53 expression with survival outcomes in oropharyngeal cancer [J]. Cancer Biomark , 2019 , 24 ( 2 ): 141 - 151 .
Awad AM , Bradley MC , Fernandez-Del-Rio L , et al . Coenzyme Q10 deficiencies: pathways in yeast and humans [J]. Essays Biochem , 2018 , 62 ( 3 ): 361 - 376 .
Bouchez C , Devin A . Mitochondrial biogenesis and mitochondrial reactive oxygen species (ROS): a complex relationship regulated by the cAMP/PKA signaling pathway [J]. Cells , 2019 , 8 ( 4 ).
Pastor-Maldonado CJ , Suarez-Rivero JM , Povea-Cabello S , et al . Coenzyme Q10: novel formulations and medical trends [J]. Int J Mol Sci , 2020 , 21 ( 22 ).
0
浏览量
342
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621
