Abstract 2566: Critical role of autophagy proteins Beclin 1 and LC3B in deguelin-induced apoptosis in pancreatic tumor cellsin vitroandin vivo: A new paradigm

2012 ◽  
Author(s):  
Srinivas Reddy Boreddy ◽  
Prabodh K. Kandala ◽  
Kartick C. Pramanik ◽  
Parul Gupta ◽  
Sanjay K. Srivastava
Keyword(s):  
Pancreatic Tumor ◽  
Critical Role ◽  
Beclin 1 ◽  
New Paradigm ◽  
Induced Apoptosis

scholarly journals The critical role of T cells in glucocorticoid-induced osteoporosis

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Lin Song ◽  
Lijuan Cao ◽  
Rui Liu ◽  
Hui Ma ◽  
Yanan Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Steady State ◽  
Side Effects ◽  
Critical Role ◽  
Wild Type ◽  
Receptor Activator ◽  
Steady State Levels ◽  
Induced Apoptosis

AbstractGlucocorticoids (GC) are widely used clinically, despite the presence of significant side effects, including glucocorticoid-induced osteoporosis (GIOP). While GC are believed to act directly on osteoblasts and osteoclasts to promote osteoporosis, the detailed underlying molecular mechanism of GC-induced osteoporosis is still not fully elucidated. Here, we show that lymphocytes play a pivotal role in regulating GC-induced osteoporosis. We show that GIOP could not be induced in SCID mice that lack T cells, but it could be re-established by adoptive transfer of splenic T cells from wild-type mice. As expected, T cells in the periphery are greatly reduced by GC; instead, they accumulate in the bone marrow where they are protected from GC-induced apoptosis. These bone marrow T cells in GC-treated mice express high steady-state levels of NF-κB receptor activator ligand (RANKL), which promotes the formation and maturation of osteoclasts and induces osteoporosis. Taken together, these findings reveal a critical role for T cells in GIOP.

scholarly journals Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Qingqiang Xu ◽  
Wenwen Shi ◽  
Pan Lv ◽  
Wenqi Meng ◽  
Guanchao Mao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Aflatoxin B1 ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Hepatic Cell ◽  
Hepatocellular Injury ◽  
Caveolin 1 ◽  
Induced Apoptosis

AbstractAflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

scholarly journals Molecular mechanisms of estrogen receptor β-induced apoptosis and autophagy in tumors: implication for treating osteosarcoma

2019 ◽  
Vol 47 (10) ◽  
pp. 4644-4655
Author(s):  
Zheng-ming Yang ◽  
Min-fei Yang ◽  
Wei Yu ◽  
Hui-min Tao
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptors ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Critical Role ◽  
Osteosarcoma Cells ◽  
Proliferation And Metastasis ◽  
Induced Apoptosis

The estrogen receptors α (ERα) and β (ERβ) are located in the nucleus and bind to estrogen to initiate transcription of estrogen-responsive genes. In a variety of tumor cells, ERβ has been shown to be a tumor suppressor. In particular, ERβ has anti-proliferative effects in osteosarcoma cells. Additionally, ERβ has been proven to regulate the apoptosis-related molecules IAP, BAX, caspase-3, and PARP, and to act on the NF-κB/BCL-2 pathway to induce apoptosis in tumors. Moreover, ERβ can regulate the expression of the autophagy associated markers LC3-I/LC-3II and p62 and induce autophagy in tumors by inhibiting the PI3K/AKT/mTOR pathway and activating the AMPK pathway. Here, we review the molecular mechanisms by which ERβ induces apoptosis and autophagy in a variety of tumors to further delineate more specific molecular mechanisms underlying osteosarcoma tumorigenesis and pathogenesis. Considering the broad involvement of ERβ in apoptosis, autophagy, and their interaction, it is plausible that the critical role of ERβ in inhibiting the proliferation and metastasis of osteosarcoma cells is closely related to its regulation of apoptosis and autophagy.

scholarly journals The Chondroprotective Role of TMF in PGE2-Induced Apoptosis Associating with Endoplasmic Reticulum Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Jianqiong Yang ◽  
Haiqing Liu ◽  
Linfu Li ◽  
Hai Liu ◽  
Weimei Shi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathways ◽  
Inflammatory Cytokine ◽  
Critical Role ◽  
Osteoarthritic Chondrocytes ◽  
Induced Apoptosis

Endoplasmic reticulum stress (ERS) has been demonstrated to exhibit a critical role in osteoarthritic chondrocytes. Whether 5,7,3′,4′-tetramethoxyflavone (TMF) plays the chondroprotective role in inhibition of PGE2-induced chondrocytes apoptosis associating with ERS has not been reported. To investigate this, the activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes pretreated with PGE2was studied. By treatment with PGE2, the chondrocytes apoptosis was significantly increased, the proapoptotic CHOP and JNK were upregulated, the prosurvival GRP78 and XBP1 were downregulated, and GSK-3βwas also upregulated. However, TMF exhibited the effectively protective functions via counteracting these detrimental effects of PGE2. Finally, the inflammatory cytokine PGE2can activate ERS signaling and promote chondrocytes apoptosis, which might be associated with upregulation of GSK-3β. TMF exhibits a chondroprotective role in inhibiting PGE2-induced ERS and GSK-3β.

Sign in / Sign up

Export Citation Format

Share Document