Loss of dynamin-related protein 1 (Drp1) does not affect epidermal development or UVB-induced apoptosis but does accelerate UVB-induced carcinogenesis

2020 ◽  
Vol 99 (2) ◽  
pp. 109-118
Author(s):  
Teruki Yanagi ◽  
Shinya Kitamura ◽  
Keisuke Imafuku ◽  
Asuka Suto ◽  
Takuya Maeda ◽  
...  
Keyword(s):  
Related Protein ◽  
Induced Apoptosis ◽  
Epidermal Development

Parathyroid hormone related protein (PTHrP) inhibits TNFα-induced apoptosis by blocking the extrinsic and intrinsic pathways

2006 ◽  
Vol 210 (2) ◽  
pp. 507-516 ◽  
Author(s):  
Liliane Okoumassoun ◽  
Diana Averill-Bates ◽  
Francine Denizeau ◽  
Janet E. Henderson
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Induced Apoptosis

scholarly journals Secreted Frizzled-Related Protein-2 Inhibits Doxorubicin-Induced Apoptosis Mediated through the Akt-mTOR Pathway in Soleus Muscle

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hilda Merino ◽  
Dinender K. Singla
Keyword(s):  
Oxidative Stress ◽  
Adverse Effects ◽  
Soleus Muscle ◽  
Therapeutic Potential ◽  
Mtor Pathway ◽  
Related Protein ◽  
Proapoptotic Protein ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Muscle Toxicity

Doxorubicin (Dox) is a potent chemotherapeutic drug known for its dose-dependent and serious adverse effects, such as cardiotoxicity and myotoxicity. Dox-induced cardiotoxicity (DIC) and muscle toxicity (DIMT) have been studied; however, the mechanisms of Dox-induced apoptosis in soleus muscle are not well defined. Our data shows that with Dox treatment, there is a significant increase in oxidative stress, apoptosis, proapoptotic protein BAX, pPTEN levels, and wnt3a and β-catenin activity (p<0.05). Moreover, Dox treatment also resulted in decreased antioxidant levels, antiapoptotic BCL2, pAKT, p-mTOR, and endogenous levels of sFRP2 in the soleus muscle tissue (p<0.05). Secreted frizzled-related protein 2 (sFRP2) treatment attenuated the adverse effects of DIMT and apoptosis in the soleus muscle, evidenced by a decrease in oxidative stress, apoptosis, BAX, pPTEN, and wnt3a and β-catenin activity, as well as an increase in antioxidants, BCL2, pAKT, p-MTOR, and sFRP2 levels (p<0.05). This data suggests that Dox-induced oxidative stress and apoptosis is mediated through both the Akt-mTOR and wnt/β-catenin pathways. Moreover, the data also shows that sFRP2 modulates these two pathways by increasing signaling of Akt-mTOR and decreased signaling of the wnt/β-catenin pathway. Therefore, our data suggests that sFRP2 has valuable therapeutic potential in reversing Dox-induced oxidative stress and apoptosis in soleus muscle mediated through the Akt-mTOR pathway.

scholarly journals The Molecular Mechanism of Endoplasmic Reticulum Stress-Induced Apoptosis in PC-12 Neuronal Cells: The Protective Effect of Insulin-Like Growth Factor I

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 277-285 ◽  
Author(s):  
Cheng-Gang Zou ◽  
Xiu-Zhen Cao ◽  
Yue-Shui Zhao ◽  
Shun-Yu Gao ◽  
Shu-De Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protective Effect ◽  
Er Stress ◽  
P38 Mapk ◽  
Neuronal Apoptosis ◽  
Neuronal Cells ◽  
Dependent Manner ◽  
Related Protein ◽  
Igf I ◽  
Induced Apoptosis

Endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative diseases. Although CCAAT/enhancer-binding protein homologous protein (CHOP) has been shown to play a critical role in ER stress, the precise apoptosis cascade downstream of CHOP is unknown. In this report, we investigated the mechanism of ER stress-mediated apoptosis as well as the action of IGF-I in PC-12 neuronal cells. Our results demonstrated that tribbles-related protein 3 (TRB3), which is a target gene of CHOP, was responsible for tunicamycin (an ER stress inducer)-induced apoptosis. TRB3 could promote dephosphorylation of Akt in PC-12 cells. IGF-I inhibited ER stress-induced apoptosis by restoring the phosphorylation level of Akt. Both wortmannin (a phosphatidylinositide 3-kinase inhibitor) and SB 212090 (a p38 MAPK inhibitor) suppressed the protective effect of IGF-I on ER stress-induced apoptosis. Interestingly, IGF-I attenuated ER stress-mediated expression of TRB3 but not CHOP. This action of IGF-I was abolished by SB 212090 but not by wortmannin. Immunoprecipitation analysis revealed that IGF-I promoted the phosphorylation of CHOP by activating p38 MAPK, probably leading to a decrease in the transcriptional activity of CHOP. The dephosphorylation of Akt resulted in increased expression of a proapoptotic protein, p53 up-regulated modulator of apoptosis (PUMA), in a forkhead box O3a-dependent manner. Knockdown of PUMA by short hairpin RNA attenuated ER stress-mediated apoptosis. Thus, our current study indicates that both TRB3 and PUMA are critical molecules in ER stress-induced apoptosis. IGF-I effectively protects PC-12 neuronal cells against ER stress-induced apoptosis through the phosphatidylinositide 3-kinase/Akt and p38 MAPK pathways. Endoplasmic reticulum (ER) stress causes neuronal apoptosis by inducing the expression of tribbles-related protein 3 and PUMA. IGF-1 prevents neuronal apoptosis against ER stress through phosphatidylinositide 3-kinase/Akt and p38 mitogen-activated protein kinase pathways.

scholarly journals Non-esterified Fatty Acid-Induced Reactive Oxygen Species Mediated Granulosa Cells Apoptosis Is Regulated by Nrf2/p53 Signaling Pathway

Antioxidants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 523
Author(s):  
Yiru Wang ◽  
Chengmin Li ◽  
Julang Li ◽  
Genlin Wang ◽  
Lian Li
Keyword(s):  
Reactive Oxygen Species ◽  
Fatty Acid ◽  
Granulosa Cells ◽  
Ovarian Function ◽  
Reactive Oxygen ◽  
Follicular Development ◽  
Oxygen Species ◽  
Related Protein ◽  
Induced Apoptosis

Negative energy balance (NEB) during the perinatal period can affect dairy cow follicular development and reduce the fecundity. Non-esterified fatty acid (NEFA) concentration is elevated during NEB, and is known to be toxic for multiple cell types. In the ovary, NEB increased NEFA, and may influences follicular growth and development. However, the effect and mechanism of NEFA on granulosa cells (GCs) in vitro remains unknown. In this study, we found that NEFA dose-dependently induced apoptosis in primary cultured granulosa cells. Mechanistically, our data showed that NEFA significantly increased reactive oxygen species (ROS) levels, resulting in the activation of endoplasmic reticulum stress (ERS) and eventually cell apoptosis in GCs. Moreover, NEFA also increased the phosphorylation levels of ERK1/2 and p38MAPK pathways, upregulated the expression of p53 and potentially promoted its translocation to the nuclear, thus transcriptionally activated Bax, a downstream gene of this pathway. NEFA also promoted nuclear factor E2 (Nrf2) expression and its level in the nuclear. To elucidate the mechanism of NEFA action, N-acetyl-l-cysteine (NAC), a ROS scavenger was used to verify the role of ROS in NEFA induced apoptosis of GCs. NAC pretreatment reversed the NEFA-induced ERS-related protein and apoptosis-related protein levels. Meanwhile, NAC pretreatment also blocked the phosphorylation of ERK1/2 and p38 induced by NEFA, and the nucleation of Nrf2 and p53, suggesting that ROS plays a crucial role in regulating the NEFA-induced apoptosis of GCs. Together, these findings provide an improved understanding of the mechanisms underlying GCs apoptosis, which could potentially be useful for improving ovarian function.

Beta-Ecdysone Protects Mouse Osteoblasts from Glucocorticoid-Induced Apoptosis In Vitro

Planta Medica ◽  
2017 ◽  
Vol 83 (11) ◽  
pp. 888-894 ◽  
Author(s):  
Wei-Wei Dai ◽  
Li-Bo Wang ◽  
Guo-Qin Jin ◽  
Hong-Jin Wu ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Ataxia Telangiectasia ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Related Protein ◽  
Ataxia Telangiectasia Mutated ◽  
Related Transcription Factor ◽  
Induced Apoptosis ◽  
Ataxia Telangiectasia Mutated Protein

AbstractGlucocorticoid-induced osteoporosis is a common form of secondary osteoporosis. Glucocorticoids affect both bone formation and resorption, and prolonged glucocorticoid exposure can suppress osteoblast activities. beta-Ecdysone, found in many plants, is involved in protein synthesis, carbohydrate and lipid metabolism, and immunologic modulation. Here, we evaluated the effects of beta-ecdysone on osteoblast viability by assessing apoptosis following treatment with excess glucocorticoids. Mouse bone marrow stromal cells were induced to differentiate and grow into osteoblasts, and then treated with 10 µM glucocorticoid and 10, 1, or 0.1 µM beta-ecdysone. The expression levels of osteoblast growth and differentiation factors (runt-related transcription factor 2, osteogenic protein-1, and alkaline phosphatase), apoptosis-related genes (transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8), and Akt1 and phospho-Akt (Thr308) were then assessed via alkaline phosphatase staining, acridine orange-propidium iodide staining, annexin V/PI apoptosis assay, real-time RT-PCR, and Western blot analyses. Notably, treatment with 10 µM glucocorticoid resulted in reduced osteoblast viability and the specific activity of alkaline phosphatase as well as reduced runt-related transcription factor 2, osteogenic protein-1, and alkaline phosphatase mRNA expression in vitro, indicating that glucocorticoid inhibited osteogenic differentiation. Moreover, glucocorticoid treatment yielded increased transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8 expression and decreased Akt1 and phospho-Akt levels, indicating glucocorticoid-induced apoptosis. Meanwhile, beta-ecdysone inhibited glucocorticoid function, preserving the expression of Akt1 and phospho-Akt and reducing the expression of transformation-related protein 53, ataxia telangiectasia mutated protein, caspase-3, and caspase-8. Thus, beta-ecdysone prevented glucocorticoid-induced osteoblast apoptosis in vitro. These data highlight the potential for beta-ecdysone as a treatment for preventing the effects of glucocorticoid on bone growth.

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