Mitochondrial Dysfunction, Immune Systems, Their Diseases, and Possible Treatments
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Chronic inflammation has been described in numerous cases as a trigger to induce more aggressive pathologies. It is for example the case in colitis-associated cancer (CAC) in which inflammasome activity is altered leading to continuous inflammation. A new small molecule, Andrographolide (Andro), has been described to inhibit NRLP3-inflammasome activity in macrophages and the release of pro-inflammatory cytokine IL-1β, and to attenuate colitis and tumor growth.79 More interestingly, Andro has been shown to induce mitophagy in macrophages and therefore to inhibit the accumulation of damaged mitochondria presenting mitochondrial membrane potential collapse. This effect was confirmed to be mitophagy-specific since Becn1 knockdown as well as autophagy inhibitors inhibited this effect. This result demonstrated that Andro inhibited NRLP3-inflammasome activity by degrading damaged mitochondria and then leading to the attenuation of CAC.
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.
Mechanisms of Hepatitis C Virus Clearance by Interferon and Ribavirin Combination
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
In order to explain why an HCV persistently infected cell culture is resistant to IFN-α and RBV combination treatment, we have examined activation of ER stress and autophagy in HCV cell culture (Chandra et al. 2014). ATF6 luciferase activity shows that persistently infected HCV culture also induces a chronic ER stress response. It is known that cellular autophagy response is activated secondary to ER stress as a cell survival defense mechanism. Induction of an autophagy response in the persistently infected HCV culture was verified by a number of autophagy assays including the processing of LC3-I into LC3-II by Western blotting and the induction of the key autophagy gene, Beclin1, in the persistently infected culture. The expression of p62 was reduced significantly in the infected cells in a time-dependent manner, which indicated that HCV replication induced an autophagy response. We also investigated whether persistent HCV replication could induce autophagosomes, which then progress to autophagolysosomes through fusion with acidic lysosomes detectable by using acridine orange staining. Considerably higher numbers of membrane localized autophagic vacuoles were observed in the persistently infected cells as compared to uninfected cells. We further verified our hypothesis that the lack of cell surface expression of IFNAR1 is the cause of IFN-α resistance by analysis of HCV-positive and HCV-negative cell populations after flow sorting. These results showed that the IFN-α-resistant cells had a notably lower level of IFNAR1 than the IFN-α-sensitive cells.
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.
Autophagy-dependent ferroptosis is involved in the development of endometriosis
Published in Gynecological Endocrinology, 2023
Hui Li, Huadi Yang, Shenyi Lu, Xinyan Wang, Xinhe Shi, Peiyu Mao
Autophagy is a cellular degradation process that removes and recycles damaged proteins and organelles through the lysosomal machinery. Initiated by the formation of a phagophore, a double-membrane structure, autophagy is mediated by various Atg proteins that control the expansion of the phagophore, resulting in an autophagosome. Several Atgs are associated with autophagy, among which LC3 and Beclin1 are significant factors [7]. LC3, a gene homologous to the Atg8 autophagy-related gene in yeast, is a unique marker of autophagosomes, and its expression level directly signifies the degree of autophagy [8]. Beclin1 also referred to as BECN 1, is an autophagy-specific gene, a tumor suppressor gene related to autophagy, and a direct autophagy regulator in mammals [9]. The autophagosome then merges with a lysosome, leading to the degradation and recycling of its content [10,11]. This process plays a pivotal role in maintaining cellular homeostasis. Dysregulation of autophagy, as has been suggested in the context of EMS, may promote the survival and proliferation of ectopic endometrial cells [3]. EMS exhibits numerous tumor disease traits, including metastasis, implantation, and recurrence [12,13]. Various studies have reported a link between autophagy and several malignant tumors. For instance, a decrease in autophagy activity has been associated with the onset and progression of various cancers, including pancreatic, breast, cervical squamous cell, colon, and ovarian cancer, indicating a strong correlation between the abnormal expression of autophagy-related genes and tumor development [14,15].
Biosynthesis of silver nanoparticles using Citrus hystrix leaf extract and evaluation of its anticancer efficacy against HeLa cell line
Published in Drug Development and Industrial Pharmacy, 2022
Swetha Srimurugan, Anjali K. Ravi, Vijaya Anand Arumugam, Saradhadevi Muthukrishnan
Cervical cancer persists as the second major malignancy among women, with an annual global incidence of 570,000 diagnosed cases and 311,000 fatalities [1]. Human papilloma virus (HPV) infection is regarded as the major causative agent for the development of cervical cancer. Other risk factors include poor hygiene conditions, smoking, oral contraceptive usage, lifestyle changes, lack of physical activity, and exposure to radiation [2]. Since the inadequate preventive screening methods and early diagnosis, cervical cancer becomes aggressive and metastasizes into various parts [3]. The autophagy and apoptosis pathways maintain cellular homeostasis, but cancer cells become resistant to these pathways via modifying the anti and pro-apoptotic proteins to induce proliferation and metastasis of cancer cells [4]. Autophagy is a dynamic process associated with the formation of autophagosome, a double-membrane cytoplasmic vesicle which engulfs the damaged cellular components. The autophagosome can combine with lysosomes to generate auto-lysosomes, which preferentially destroy damaged cellular organelles and proteins by interacting with phosphatidyl ethanolamine, ATG 3, and ATG7 [5]. In normal circumstances, Beclin1 initiates autophagy by recruiting several autophagy-related complex proteins involved in autophagosome initiation and elongation. These protein complexes attract LC-3 I, which then transforms into LC-3 II [6].
Related Knowledge Centers
- Cell Death
- Programmed Cell Death
- Protein
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- Autophagy
- Carcinogenesis
- Gene
- BCL-2
- Phosphoinositide 3-Kinase
- Neurodegenerative Disease