Bone Regeneration Effect of Cassia occidentalis Linn. Extract and Its Isolated Compounds
Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay in Phytochemistry of Plants of Genus Cassia, 2021
The anti-oxidant effect of kaempferol in osteoblasts has been studied. 2-Deoxy-D-ribose (dRib) is a sugar with a high reducing capacity and induces oxidative stress and kaempferol mitigates dRib-induced oxidative stress in MC3T3-E1 cells by reducing malondialdehyde content (Suh et al., 2009). Kaempferol is also known to activate both ERα- and ERβ transactivation and promote the expression of osteogenic genes (Guo et al., 2012; Tang et al., 2008). In MC3T3-E1 cells, induction of differentiation by kaempferol was accompanied by autophagy assessed by the expression of beclin-1, sequestosome-1, and conversion of LC3-II to LC3-I (Kim et al., 2016). Kaempferol also protects osteoblasts against dexamethasone-induced apoptosis through the activation of the ERK pathway (Adhikary et al., 2018). Together the data suggest that kaempferol promotes osteogenic differentiation, protects against oxidative stress, and drug-induced apoptosis. The signaling mechanisms are varied including ER, BMP, mTOR and autophagy pathways.
Lung cancer inhalation therapeutics
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
Several investigators have successfully delivered genes by inhalation using these nonviral carriers. Inhalation of p53 tumor suppressor gene in lipoplexes containing polylysine and protamine reduced lung metastasis in a murine model of malignant melanoma (167). Likewise, upregulation of beclin-1, a tumor suppressor gene involved in autophagy, sensitized tumor cells to radiation therapy (168). Another approach involves transfection of tumors with a gene that codes for a specific enzyme that transforms a benign drug into a toxic metabolite that causes cell death (“suicide gene”). For example, transduction of herpes simplex virus 1 thymidine kinase (HSVtk) gene makes cells susceptible to ganciclovir, a nucleoside analogue, which is normally poorly metabolized by mammalian cells. HSVtk converts ganciclovir to a metabolite that causes cell death by interfering with DNA replication. Clinical trials have employed an adenoviral vector to transduce HSVtk by intratumoral injection into mesothelioma with partial success (169). Inhalation of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor gene with glycosylated conjugated PEI resulted in expression of a functional PTEN protein in the lung with reduced phosphorylation of its target protein and apoptosis in transduced lung cells (170).
Role of Vitamin D and Antioxidant Functional Foods in the Prevention and Treatment of Alzheimer’s Disease Pathology
Abhai Kumar, Debasis Bagchi in Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Mediators of apoptosis involved in AD disease include c-jun (the protein encoded by the JUN gene that forms the AP-1 early response transcription factor), BCL2 (apoptosis regulator B-cell lymphoma 2 protein), and BCL-xL (B-cell lymphoma-extra-large, apoptosis-related transmembrane molecule in the mitochondria). A decrease in BLC2 is observed in NFT and an increase in Bax (apoptosis regulator) is observed in neurons of some microglia in AD brains. Some of the caspases involved include caspases 3/6 and 9 which can be associated with misfolded tau. Even though apoptosis is a contributor to the cell death observed in AD, it is not confirmed that it is responsible for all death observed with this disease. Apoptosis may not be significantly increased in AD animal disease models. In humans, necrosis is also an important contributor to AD cell death. One mechanism thought to be relevant in neuronal loss synaptic loss is nonapoptotic sublethal caspase activation in the dendrite’s axons. Inhibition of apoptosis protein and proteasome activity may have a role in leading the cell fat into a nonapoptotic pathway. Beclin-1 (protein encoded by the BECN1 gene) expression is decreased in human brains during aging and reduces beta-amyloid pathology in APP mice.
Roles of Beclin1 protein expression in cervical cancer: a meta-analysis and bioinformatics analysis
Published in Journal of Obstetrics and Gynaecology, 2022
Guan-Ying Ma, Shuai Shi, Hong-Yan Ma, Zhi-Gang Zhang
Beclin1 is a tumour suppressor gene, so the higher the expression level of Beclin1, the better the prognosis of tumours, and plays a significant part in the development of tumour diseases (Stang 2010; Wang J et al. 2017; Wang YY et al. 2017). Beclin1 is a gene that positively regulates autophagy and can regulate the process of autophagy. Beclin1 suppresses tumours primarily by blocking mutations in cancer-related genes. It can induce autophagy apoptosis of tumour cells. It can inhibit the angiogenesis of tumour tissue (Duan and Peng 2011). Cheng et al. conducted an in vitro culture of cervical cancer cells with rectal metastases and found that Beclin1 was able to inhibit the metastasis and invasion of the metastatic cell line HeLa cells, suggesting that the inhibitory effect of Beclin1 on cell proliferation was relevant (Cheng YX et al. 2016). Although there are few studies on Beclin1 expression in cervical cancer at home and abroad, some studies have found that Beclin1 protein expression is decreased in brain tumours, lung cancer, ovarian cancer, breast cancer and endometrioid adenocarcinoma, especially the progression and prognosis of cervical cancer is associated with decreased Beclin1 expression level (Cerit et al. 2018). Studies have shown that the positive rate of Beclin1 in cervical cancer tissues, cervical squamous intraepithelial lesions and normal mucosa increases successively, and Beclin1 gene inhibits the formation and development of cervical cancer, which has a certain correlation with its prognosis (Liu C et al. 2013). This is consistent with the trend of the results of our experimental analysis.
Uric acid and sphingomyelin enhance autophagy in iPS cell-originated cardiomyocytes through lncRNA MEG3/miR-7-5p/EGFR axis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Yinyin Cao, Junxiang Wen, Yang Li, Weicheng Chen, Yao Wu, Jian Li, Guoying Huang
Since UA and SM were two potential VSD-associated metabolites that were significantly elevated in the serum, we aimed to determine the effects of combinational treatment of UA and SM on cardiomyocytes. In this study, iPS cell-derived cardiomyocytes were used as the cell model, as described in our previous report [15]. We observed the combination of UA and SM promoted autophagy in cardiomyocytes by TEM assessment (Figure 2(D)). Next, a group of autophagy protein markers was applied to determine the level of autophagy by Western blots. In addition to p62, we added two other autophagy markers beclin-1 and Atg7 to evaluate autophagic level. Beclin-1 is an essential regulator of autophagy and exerts important roles in the initiation of autophagosome formation [30]. As a multifunctional regulator in autophagy, Atg7 is critical for autophagosome formation and promotes maturation of Atg8 (LC3) from an immature cytosolic form to an autophagosomal membrane protein [31,32]. In our study, we found that p62 level was decreased while beclin-1 and Atg7 were increased in UA and SM-treated cardiomyocytes, indicating the formation of autophagosomes was enhanced (Figure 2(E)).
The role of autophagy and mitophagy in cancers
Published in Archives of Physiology and Biochemistry, 2022
Hong-Ming Xu, Fei Hu
Beclin1 (BECN1), which is an ortholog of the Atg6/vacuolar protein sorting (Vps)-30 protein in yeast, plays a major role in the critical step of the autophagic process by interacting with class III-type phosphoinositide 3-kinase (Class III PI3K, also known as Vps34). The activation of the kinase activity of the Beclin1-Vps34 complex promotes the production of phosphatidylinositol 3-phosphate, thereby promoting cargo recruitment, lipid membrane extension and autophagosome maturation (Kihara et al.2001). Beclin1 and Vps34 form two distinct complexes. The Beclin1-Vps34 complex I, in which Atg14L cross-links between Beclin1 and the Vps34-p150 complex, mediates autophagosome formation. Beclin1-Vps34 complex II, in which Beclin1 and the Vps34-p150 complex are bridged by UVRAG, regulates the vacuolar protein-sorting pathway (Itakura et al.2008). Some endogenous factors, including transcriptional factors and microRNAs, modulate autophagy during pressure overload (PO) by regulating Beclin1 levels (Yin et al.2013). Cardiac pressure overload, such as those caused by aortic stenosis and systemic hypertension, commonly results in cardiac hypertrophy, and may lead to the development of heart failure. Hypertrophic stimuli, such as PO and angiotensin II, downregulate miR-30a, which stimulates autophagy through the upregulation of Beclin1 (Yin et al.2013). The overexpression of Beclin1 in breast cancer cells promotes autophagy and inhibits the malignant phenotype (Qu et al.2003).
Related Knowledge Centers
- Cell Death
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- BCL-2
- Phosphoinositide 3-Kinase
- Neurodegenerative Disease