Apoptotic Effect of Gentamicin in Cochlea Ototoxic Rat Model (Preliminary Study)
Cut Adeya Adella in Stem Cell Oncology, 2018
In this study, the pro-apoptotic role of gentamicin as shown in the apoptotic index of the fibroblasts of ototoxic rat models was evaluated. Gentamicin at a dosage of 40 mg/ml was enough to increase the apoptotic index in lateral cochlear wall fibroblasts. Gentamicin toxicity enhances stress markers (caspase 12), pro-apoptotic BAX, released caspase 3 and blocked anti-apoptotic Bcl-2 (Jaikumkao et al., 2016). In chinchillas exposed to gentamicin it was found that cochlea cell death markers increased (Ding et al., 2010). In this present study the method of intratympanic gentamicin injection dose to a Wistar rat used in other research (Sagit et al., 2013) was followed. The chosen termination time of 18 hours after exposure was based on the results of a study of the round window membrane in guinea pigs, which gave the best TUNEL results (Suzuki et al., 2008).
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Hala Gali-Muhtasib, Racha Chouaib in Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Apoptosis is an energy-dependent process. Two main apoptotic signaling pathways, including the extrinsic death receptor pathway and the intrinsic mitochondrial pathway, have been well-characterized. However, there are additional pathways that involve the T-cell-mediated cytotoxicity and the perforin-granzyme pathway. The perforin/granzyme pathway induces apoptosis through either granzyme B or granzyme A. Another recent pathway of apoptosis is mediated by the endoplasmic reticulum (ER) which plays important roles in cell fate and will be discussed in details later [17]. Apoptosis is mediated by chronological activation of protein superfamily of caspases [16]. Caspases are expressed in an inactive form of proenzymes in most cells. When activated, they activate other procaspases, leading to the initiation of the cascade of caspase-dependent apoptosis pathway. Caspases are highly conserved cysteine-dependent aspartate-specific proteases. There are different types of caspases: initiator caspases, including CASP-2, 8, 9, and 10; effector caspases, such as CASP-3, 6, and 7; and inflammatory caspases which are CASP-1, 4, and 5). The other caspases that have been recently studied are (i) caspase-11, which is involved in the regulation of apoptosis and cytokine maturation during septic shock, (ii) caspase-12, which mediates apoptosis through the endoplasmic reticulum, (iii) caspase-13, which is believed to be a bovine gene, and (iv) caspase-14, which is highly expressed just in embryonic tissues [23]. Initiator caspases are inactive until specific oligomeric activator protein binds to them. Subsequently, they bind to effector caspases. Effector caspases are then activated through proteolytic cleavage. The activated caspases then proteolytically degrade the intracellular proteins necessary for programmed cell death.
Therapeutic Options to Enhance Poststroke Recovery in Aged Humans
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
At tissue level one, a clear effect of hypothermia was the preservation of the infarct core, suggesting that the phagocytic activity of microglia was diminished in the animals kept under hypothermic conditions in the first 2 days poststroke. At the transcription level, hypothermia caused a reduction in the mRNA coding for caspase 12, NF-kappa B, and grp78 in the peri-infarcted region, suggesting an overall decrease in the transcriptional activity related to inflammation and apoptosis [62].
The protective effect of decoction of Rehmanniae via PI3K/Akt/mTOR pathway in MPP+-induced Parkinson's disease model cells
Published in Journal of Receptors and Signal Transduction, 2021
We have shown that DOR inhibited the SH-SY5Y cells apoptosis induced by MPP+. Hence, we further studied the apoptosis-related proteins and Caspase-12 apoptosis pathway in SH-SY5Y cells. According to the experimental data, Bax and Cyt-c expressions in MPP+ group were significantly higher than control, while those in MPP+-induced SH-SY5Y cells were obviously reduced by DOR in a dose-dependent manner. However, MPP+ markedly reduced the Bcl-2 expression in SH-SY5Y cells, while DOR evidently up-regulated the expression level of Bcl-2 (Figure 5(A,B); p < .05). Moreover, MPP+ and DOR also affected the Caspase-12 apoptosis pathway in SH-SY5Y cells. The cleaved Caspase-12, cleaved Caspase-9, and cleaved Caspase-3 expressions in SH-SY5Y cells were significantly up-regulated by MPP+. After treatment with different concentrations of DOR, the cleaved Caspase-12, cleaved Caspase-9, and cleaved Caspase-3 expressions in MPP+-induced SH-SY5Y cells were greatly reduced (Figure 5(C); p < .05). Hence, MPP+ could activate the expressions of Caspase-12, Caspase-9, and Caspase-3 in SH-SY5Y cells, while DOR reduced the Caspase-12 apoptosis pathway expression in MPP+-induced SH-SY5Y cells. According to these results, we speculated that DOR inhibited apoptosis of MPP+-induced SH-SY5Y cells through affecting the expression levels of apoptosis-related proteins and Caspase-12 apoptosis pathway.
Role of the mitochondrial calcium uniporter in Mg2+-free-induced epileptic hippocampal neuronal apoptosis
Published in International Journal of Neuroscience, 2020
Yingjiao Li, Cui Wang, Yajun Lian, Haifeng Zhang, Xianghe Meng, Mengyan Yu, Yujuan Li, Nanchang Xie
Endoplasmic reticulum (ER) stress is a cellular stress state that is caused by various conditions that interfere with the balance of the intracellular environment, including oxidative stress [6]. ER stress promotes glucose-regulated protein 78 (GRP78) dissociation and activates the unfolded protein response to restore ER function. However, if the damage is too severe, downstream apoptotic signal molecules such as C/-EBP homologous protein (CHOP) and cysteinyl aspartate-specific proteinase 12 (caspase 12) are activated, leading to cell apoptosis [7, 8]. Mitochondrial Ca2+ overload leads to increased production of ROS and oxidative stress, which is an important inducer of ER stress [9, 10]. However, the effect of the MCU on ER stress in epileptic neuronal injury is still elusive.
Dexmedetomidine Ameliorates Post-CPB Lung Injury in Rats by Activating the PI3K/Akt Pathway
Published in Journal of Investigative Surgery, 2020
Jian Li, Xuejiao Dou, Dongdong Li, Miao He, Ming Han, Hong Zhang
Apoptosis plays an important role in balancing cell proliferation and death [14]. The regulation of apoptosis depends on the death receptor pathway, the mitochondrial pathway, and the endoplasmic reticulum pathway. In the endoplasmic reticulum stress state, caspase-12 zymogen is specifically activated by other endoplasmic reticulum stress molecules, which leads to apoptosis by way of the caspase-3 pathway [15]. The caspase family contains some of the most important downstream effectors of the PI3K/Akt signaling pathway, which are mainly present in living cells in the form of inactive zymogens, and which play an essential role in apoptosis with caspase-9 acting as a promoter, and caspase-3 acting as an effector. It has been shown that the PI3K/Akt signaling pathway regulates the apoptotic cycle by inhibiting the activity of the caspase family [16].