scholarly journals Shen Shuai II Recipe Attenuates Apoptosis in 5/6 Renal Ablation/Infarction Rats by Inhibiting p53 and the Mitochondrial Pathway of Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Meng Wang ◽  
Jing Yang ◽  
Chen Wang
Keyword(s):  
Renal Injury ◽  
Molecular Mechanisms ◽  
Mitochondrial Pathway ◽  
Apoptosis Pathway ◽  
Mortality And Morbidity ◽  
Mitochondrial Apoptosis Pathway ◽  
Mitochondrial Translocation ◽  
Chinese Herbal ◽  
Renal Ablation ◽  
Critical Process

Background. Chronic kidney disease (CKD) is a global health burden with high mortality and morbidity. Clinical efficacy has been demonstrated for Shen Shuai II Recipe (SSR), an approved and widely used Chinese herbal medicine for over 20 years in China, to attenuate CKD progression. In this study, we explored the underlying molecular mechanisms of SSR benefits and studied its effects on apoptosis, a critical process in CKD development and progression. CKD was induced in rats with 5/6 renal ablation and infarction (A/I). Eight weeks after SSR treatment, we mainly assessed the severity of renal injury and fibrosis, the translocation of apoptotic factors in the mitochondrial apoptosis pathway, the degree of mitochondrial dysfunction, and the nuclear and mitochondrial translocation of p53. Furthermore, we detected the interaction of p53 with antiapoptotic Bcl-xL and Bcl-2 proteins. Our results showed that SSR significantly attenuated renal injury and fibrosis and inhibited the mitochondrial accumulation of proapoptotic proteins Bax and Puma and release of cytochrome c from mitochondria to the cytosol in a rat CKD model. In addition, SSR also improved the mitochondrial function and inhibited the nuclear and mitochondrial translocation of p53. In addition, SSR suppressed the p53 transactivation and the interaction of p53 with Bcl-xL and Bcl-2. These results suggested that SSR could block apoptosis in CKD by inhibiting p53 transcriptional-dependent and transcriptional-independent proapoptotic function and the mitochondrial pathway of apoptosis.

scholarly journals Shen Shuai II Recipe attenuates apoptosis in 5/6th renal ablation/infarction rats by inhibiting p53 and mitochondrial pathway of apoptosis

2019 ◽  
Author(s):  
Meng Wang ◽  
Jing Yang ◽  
Liuyi Yang ◽  
Chen Wang
Keyword(s):  
Underlying Mechanism ◽  
Mitochondrial Pathway ◽  
Global Public Health ◽  
Sprague Dawley ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Mitochondrial Translocation ◽  
Renal Ablation ◽  
Losartan Group ◽  
Group 5

Abstract Background Chronic kidney disease (CKD) has become a serious challenge to global public health. Apoptosis is closely related to the evolution of CKD. In China, it has been noted that Chinese herbal medicine may be suitable for the treatment of CKD. Shen Shuai II Recipe (SSR) is a classic formula for the treatment of CKD in the clinic and proves the renprotective effects. However, the underlying mechanism remains unclear. The main purpose of this study was to investigate whether SSR could reduce apoptosis in 5/6 renal ablation/infarction (A/I) hypoxia model by regulating p53 and mitochondrial pathway of apoptosis.Methods 28 days after the 5/6 (A/I) surgery, Sprague-Dawley rats were randomly divided into four groups: sham group, 5/6 (A/I) group, 5/6 (A/I) + SSR group and 5/6 (A/I) +Losartan group (5/6 (A/I) +LOR). After 56 days of treatment, we mainly assessed the translocation of apoptotic factors in mitochondrial apoptosis pathway, the degree of mitochondrial dysfunction and the nuclear and mitochondrial translocation of p53. Furthermore, we detected the interaction of p53 with anti-apoptotic Bcl-xL and Bcl-2 proteins.Results SSR significantly inhibited the mitochondrial accumulation of pro-apoptotic protein Bax and Puma and release of cytochrome c from mitochondria to cytosol in the 5/6 (A/I) model. In addition, SSR improved the mitochondrial function and inhibited the nuclear and mitochondrial translocation of p53. SSR suppressed the p53 transactivation and the interaction of p53 with Bcl-xL and Bcl-2.Conclusions These results suggested that SSR could exert anti-apoptotic effects in the 5/6 (A/I) hypoxia model by inhibiting p53 transcriptional dependent and independent pro-apoptotic functions and the mitochondrial pathway of apoptosis.

scholarly journals Lycium barbarumPolysaccharides Protect Rat Corneal Epithelial Cells against Ultraviolet B-Induced Apoptosis by Attenuating the Mitochondrial Pathway and Inhibiting JNK Phosphorylation

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Shaobo Du ◽  
Biao Han ◽  
Kang Li ◽  
Xuan Zhang ◽  
Xueli Sha ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Underlying Mechanism ◽  
Mitochondrial Pathway ◽  
Ultraviolet B ◽  
Lycium Barbarum ◽  
Apoptosis Pathway ◽  
Corneal Epithelial ◽  
Mitochondrial Apoptosis Pathway ◽  
Induced Apoptosis

Lycium barbarumpolysaccharides (LBPs) have been shown to play a key role in protecting the eyes by reducing the apoptosis induced by certain types of damage. However, it is not known whether LBPs can protect damaged corneal cells from apoptosis. Moreover, no reports have focused on the role of LBPs in guarding against ultraviolet B- (UVB-) induced apoptosis. The present study aimed to investigate the protective effect and underlying mechanism of LBPs against UVB-induced apoptosis in rat corneal epithelial (RCE) cells. The results showed that LBPs significantly prevented the loss of cell viability and inhibited cell apoptosis induced by UVB in RCE cells. LBPs also inhibited UVB-induced loss of mitochondrial membrane potential, downregulation ofBcl-2, and upregulation ofBaxand caspase-3. Finally, LBPs attenuated the phosphorylation of c-Jun NH2-terminal kinase (JNK) triggered by UVB. In summary, LBPs protect RCE cells against UVB-induced damage and apoptosis, and the underlying mechanism involves the attenuation of the mitochondrial apoptosis pathway and the inhibition of JNK phosphorylation.

scholarly journals Exendin-4 Promotes Survival of Mouse Pancreaticβ-Cell Line in Lipotoxic Conditions, through the Extracellular Signal-Related Kinase 1/2 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jianqiu Gu ◽  
Qian Wei ◽  
Hongzhi Zheng ◽  
Xin Meng ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Cell Mass ◽  
Mitochondrial Pathway ◽  
Apoptosis Pathway ◽  
Min6 Cells ◽  
Mitochondrial Apoptosis Pathway ◽  
Extracellular Signal

Type 2 diabetes is a heterogeneous disorder that develops as a result of relatively inappropriate insulin secretion and insulin resistance. Increased levels of free fatty acids (FFAs) are one of the important factors for the pathogenesis of type 2 diabetes and contribute to defectiveβ-cell proliferation and increasedβ-cell apoptosis. Recently, glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to possess an antiapoptotic effect, by increasingβ-cell mass and improvingβ-cell function. However, their effects onβ-cells in vitro against lipotoxicity have not been elucidated completely. In this study, we investigated whether the GLP-1 receptor agonist exendin-4 displays prosurvival effects in pancreaticβ-cells exposed to chronic elevated FFAs. Results showed that exendin-4 inhibited apoptosis induced by palmitate in MIN6 cells. After 24 h of incubation, exendin-4 caused rapid activation of extracellular signal-related kinase 1/2 (ERK1/2) under lipotoxic conditions. The ERK1/2 inhibitor PD98059 blocked the antilipotoxic effect of exendin-4 on MIN6 cells. Exendin-4 also inhibited the mitochondrial pathway of apoptosis. This inhibition is associated with upregulation of BCL-2. Our findings suggested that exendin-4 may exert cytoprotective effects through activation of ERK1/2 and inhibition of the mitochondrial apoptosis pathway.

scholarly journals Deoxynivalenol induces caspase-8-mediated apoptosis through the mitochondrial pathway in hippocampal nerve cells of piglet

2019 ◽  
Author(s):  
Jinjie Wu ◽  
Xichun Wang ◽  
Yunjing Jiang ◽  
Lei Zhu ◽  
Li Cao ◽  
...  
Keyword(s):  
Mitochondrial Pathway ◽  
Nerve Cells ◽  
Caspase 8 ◽  
Trichothecene Mycotoxin ◽  
Apoptotic Pathway ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Transcriptional Changes ◽  
Apoptosis Regulation

Abstract Background: Deoxynivalenol (DON) is a common trichothecene mycotoxin found throughout the world. DON has broad toxicity in animals and humans. Its neurotoxicity in vitro, however, is still unclear. This study was designed to investigate the hypothesis that DON toxicity in neurons occurs via the mitochondrial apoptotic pathway. Results: Using piglet hippocampal nerve cells (PHNCs), we evaluated the effects of varying concentrations of DON on typical indicators of apoptosis. The results obtained demonstrated that DON treatment inhibited PHNC proliferation and led to morphological, biochemical, and transcriptional changes consistent with apoptosis, including decreased mitochondrial membrane potential, mitochondrial release of CYCS and AIF, and increased abundance of active cleaved-caspase-9 and cleaved-caspase-3. Increasing concentrations of DON led to decreased Bcl-2 expression and increased expression of Bax and Bid, which in turn increased transcriptional activity of the transcription factors AIF and P53. Addition of a caspase-8 inhibitor abrogated these effects. Conclusion: These data reveal that DON induces apoptosis in PHNCs via the mitochondrial apoptosis pathway, and that caspase-8 plays an important role during apoptosis regulation.

Influence of Ca2+ on mitochondrial apoptosis activation and yak meat tenderization during postmortem aging

2021 ◽  
pp. 1-12
Author(s):  
Lin-lin Wang ◽  
Lian-hong Chen ◽  
Jian Li ◽  
Rong-sheng Du ◽  
Ling Han ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Citrate Synthase ◽  
Control Group ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Atp Production ◽  
Mitochondrial Apoptosis Pathway ◽  
Mitochondrial Functions ◽  
Postmortem Aging ◽  
Meat Tenderization

The objective of this study was to investigate the underlying molecular mechanisms of mitochondrial Ca2+ homeostasis disequilibrium in mitochondrial apoptosis and its impact on yak meat tenderness. Results indicated that CaCl2 treatment significantly promoted glycolysis by increasing lactic acid level and decreasing glycogen content, pH, and ATP production (P < 0.01 and P < 0.05). The activities of Na+-K+-ATPase pump and Ca2+-ATPase pump in the early aging stage were significantly influenced by CaCl2 treatment. The activities of synchronous digital hierarchy and citrate synthase were also significantly improved by CaCl2 treatment (P < 0.01 and P < 0.05). Mitochondrial reactive oxygen species (ROS) levels were significantly higher in the CaCl2 group than in the control group (P < 0.01); at 24 h, the value in the Ca2+ group was 64.27% higher than that in the control group. Furthermore, CaCl2 treatment significantly enhanced the mitochondrial apoptosis cascade reaction and meat tenderization by improving the myofibril fragmentation index and shear force (P < 0.01). These results demonstrated that the imbalance of mitochondrial Ca2+ homeostasis played a significant role in the mitochondrial apoptosis pathway by regulating energy metabolism factors, meat intracellular environment, mitochondrial functions, and ROS-mediated oxidative stress. These conditions further improved meat tenderization during postmortem aging.

Albicanol antagonizes Cd-induced apoptosis through a NO/iNOS-regulated mitochondrial pathway in chicken liver cells

2021 ◽  
Author(s):  
Yalin Guan ◽  
Xia Zhao ◽  
Nuan Song ◽  
Yuan Cui ◽  
Ying Chang
Keyword(s):  
Free Radical ◽  
Mitochondrial Pathway ◽  
Liver Cells ◽  
Chicken Liver ◽  
Mitochondrial Apoptosis ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Induced Apoptosis

Albicanol can reduce the excessive production of the NO free radical induced by Cd, and then inhibits the mitochondrial apoptosis pathway.

scholarly journals Pharmacological inhibition of GSK3 attenuates DNA damage-induced apoptosis via reduction of p53 mitochondrial translocation and Bax oligomerization in neuroblastoma SH-SY5Y CELLS

2013 ◽  
Vol 18 (1) ◽  
Author(s):  
Patchara Ngok-Ngam ◽  
Piyajit Watcharasit ◽  
Apinya Thiantanawat ◽  
Jutamaad Satayavivad
Keyword(s):  
Dna Damage ◽  
Cytochrome C ◽  
Glycogen Synthase ◽  
Mitochondrial Pathway ◽  
Parp Cleavage ◽  
Wild Type ◽  
Apoptosis Pathway ◽  
Apoptotic Signaling ◽  
Mitochondrial Translocation ◽  
Wild Type P53

AbstractGlycogen synthase kinase-3 (GSK3) and p53 play crucial roles in the mitochondrial apoptotic pathway and are known to interact in the nucleus. However, it is not known if GSK3 has a regulatory role in the mitochondrial translocation of p53 that participates in apoptotic signaling following DNA damage. In this study, we demonstrated that lithium and SB216763, which are pharmacological inhibitors of GSK3, attenuated p53 accumulation and caspase-3 activation, as shown by PARP cleavage induced by the DNA-damaging agents doxorubicin, etoposide and camptothecin. Furthermore, each of these agents induced translocation of p53 to the mitochondria and activated the mitochondrial pathway of apoptosis, as evidenced by the release of cytochrome C from the mitochondria. Both mitochondrial translocation of p53 and mitochondrial release of cytochrome C were attenuated by inhibition of GSK3, indicating that GSK3 promotes the DNA damage-induced mitochondrial translocation of p53 and the mitochondrial apoptosis pathway. Interestingly, the regulation of p53 mitochondrial translocation by GSK3 was only evident with wild-type p53, not with mutated p53. GSK3 inhibition also reduced the phosphorylation of wild-type p53 at serine 33, which is induced by doxorubicin, etoposide and camptothecin in the mitochondria. Moreover, inhibition of GSK3 reduced etoposide-induced association of p53 with Bcl2 and Bax oligomerization. These findings show that GSK3 promotes the mitochondrial translocation of p53, enabling its interaction with Bcl2 to allow Bax oligomerization and the subsequent release of cytochrome C. This leads to caspase activation in the mitochondrial pathway of intrinsic apoptotic signaling.

scholarly journals Cephalotaxine Inhibits the Survival of Leukemia Cells by Activating Mitochondrial Apoptosis Pathway and Inhibiting Autophagy Flow

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2996
Author(s):  
Tingting Liu ◽  
Qiang Guo ◽  
Shuze Zheng ◽  
Yang Liu ◽  
Heng Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Leukemia Cells ◽  
Mitochondrial Apoptosis ◽  
Rna Seq ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Change Mechanism ◽  
Function Change ◽  
Mechanism Research ◽  
Natural Alkaloid

Cephalotaxine (CET) is a natural alkaloid with potent antileukemia effects. However, its underlying molecular mechanism has not been well understood. In this study, we verified that CET significantly inhibited the viability of various leukemia cells, including HL-60, NB4, Jurkat, K562, Raji and MOLT-4. RNA-sequencing and bioinformatics analysis revealed that CET causes mitochondrial function change. Mechanism research indicated that CET activated the mitochondrial apoptosis pathway by reducing the mitochondrial membrane potential, downregulating anti-apoptotic Bcl-2 protein and upregulating pro-apoptotic Bak protein. In addition, the autophagy signaling pathway was highly enriched by RNA-seq analysis. Then, we found that CET blocked the fluorescence colocation of MitoTracker Green and LysoTracker Red and upregulated the level of LC3-II and p62, which indicated that autophagy flow was impaired. Further results demonstrated that CET could impair lysosomal acidification and block autophagy flow. Finally, inhibiting autophagy flow could aggravate apoptosis of HL-60 cells induced by CET. In summary, this study demonstrated that CET exerted antileukemia effects through activation of the mitochondria-dependent pathway and by impairing autophagy flow. Our research provides new insights into the molecular mechanisms of CET in the treatment of leukemia.

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