Akt-GSK3β-mPTP pathway regulates the mitochondrial dysfunction contributing to odontoblasts apoptosis induced by glucose oxidative stress.
Akt-GSK3β-mPTP pathway regulates the mitochondrial dysfunction contributing to odontoblasts apoptosis induced by glucose oxidative stress.
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Akt-GSK3β-mPTP 通路调节线粒体功能障碍，导致葡萄糖氧化应激诱导的成牙本质细胞凋亡
DOI：
10.1038/s41420-022-00981-y
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发表时间：
2022-04-05
影响因子：
7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Wu D;Yan L;Zheng C;Ren X;Pan Y;Huang S;Pan L;Li Z
糖尿病可通过氧化应激导致牙髓细胞凋亡，影响牙髓组织的完整性和功能。线粒体是氧化应激的主要攻击目标，在细胞凋亡中发挥着关键作用。然而，线粒体是否参与糖尿病引起的牙髓损伤尚不清楚。本研究旨在探讨线粒体在葡萄糖氧化应激诱导的成牙本质细胞样细胞系（mDPC6T）凋亡中的作用，并探讨其可能的机制。我们利用葡萄糖氧化酶/葡萄糖建立了体外氧化应激模型来模拟糖尿病条件下的病理状态。我们发现，线粒体通透性转换孔（mPTP）的开放导致了用葡萄糖氧化酶处理的mDPC6T的凋亡，线粒体活性氧（mtROS）增强和细胞内Ca2+紊乱，显着降低了线粒体膜电位（MMP）和ATP产生证明了这一点。抗氧化剂 N-乙酰半胱氨酸 (NAC) 或环孢菌素 A（mPTP 抑制剂）可阻断 mPTP 开放，从而显着减弱葡萄糖氧化应激诱导的线粒体功能障碍和细胞凋亡。此外，我们发现葡萄糖氧化应激刺激mPTP开放可能是通过抑制Akt-GSK3β通路来实现的。该研究为糖尿病相关成牙本质细胞样细胞凋亡的线粒体机制提供了新的见解，为糖尿病相关牙髓损伤的预防和治疗奠定了基础。
Diabetes Mellitus can cause dental pulp cells apoptosis by oxidative stress, and affect the integrity and function of dental pulp tissue. Mitochondria are the main attack targets of oxidative stress and have a critical role in apoptosis. However, whether mitochondria are involved in dental pulp damage caused by diabetes mellitus remains unclear. This study aimed to investigate the role of mitochondria in the apoptosis of odontoblast-like cell line (mDPC6T) induced by glucose oxidative stress, and to explore its possible mechanism. We established an oxidative stress model in vitro using glucose oxidase/glucose to simulate the pathological state under diabetic conditions. We found that the opening of mitochondrial permeability transition pore (mPTP) contributed to the apoptosis of mDPC6T treated with glucose oxidase, as evidenced by enhanced mitochondrial reactive oxygen species (mtROS) and intracellular Ca2+ disorder, significantly reduced mitochondrial membrane potential (MMP) and ATP production. Antioxidant N-acetylcysteine (NAC) or Cyclosporine A (mPTP inhibitor) blocked the mPTP opening, which significantly attenuated mitochondrial dysfunction and apoptosis induced by glucose oxidative stress. In addition, we found that glucose oxidative stress stimulated mPTP opening may through inhibition of Akt-GSK3β pathway. This study provides a new insight into the mitochondrial mechanism underlying diabetes-associated odontoblast-like cell apoptosis, laying a foundation for the prevention and treatment of diabetes-associated pulp injury.
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影响因子：
3.4
作者：
Chen ZR;Ma Y;Guo HH;Lu ZD;Jin QH
通讯作者：
Jin QH
影响因子：
4.2
作者：
Kermani, Mahzad Tavakolinejad;Sanjari, Mojgan;Abbott, Paul
通讯作者：
Abbott, Paul
影响因子：
64.8
作者：
Nakagawa, T;Shimizu, S;Tsujimoto, Y
通讯作者：
Tsujimoto, Y
影响因子：
7.4
作者：
Huang, S. B.;Jin, X.;Pan, Y. H.
通讯作者：
Pan, Y. H.
影响因子：
--
作者：
Liu, Lerong;Zhang, Lingxiao;Zhao, Tongfeng
通讯作者：
Zhao, Tongfeng