Autophagy: Cell death or survive mechanism

Sever, Özlem Nuray; Demir, Osman

doi:10.1016/j.jons.2017.07.001

Cited by 17 publications

(30 citation statements)

References 55 publications

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“…In the AF A , theca cells showed increased labeling for autophagic proteins, but they were weakly stained for Ctsd, possibly because these cells did not perform phagocytosis. The low vascularization of the theca during most of the follicular regression (Miranda et al, 1999) may justify the induction of autophagy to maintain cell homeostasis through clearance and selective removal of protein aggregates and dysfunctional organelles (Ryter, Cloonan, & Choi, 2013;Sever & Demir, 2017). However, under prolonged metabolic stress, autophagy may contribute to the provision of energy for apoptotic execution (Chiarelli, Agnello, Bosco, & Roccheri, 2014;Kriel & Loos, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagy is a complex catabolic mechanism involving the transport of cytoplasmic components to the lysosome (Sever & Demir, 2017). Key proteins of the autophagic pathway, such as Beclin1 and microtubule-associated protein light chain 3 (Lc3), are conserved among species and are widely used as autophagic markers (Chifenti et al, 2013;Mathai, Meijer, & Simonsen, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Under nonlethal stress, autophagy may precede apoptosis, avoiding local inflammation, but in some conditions, autophagy may lead to cell death by apoptosis with caspase-8 activation and degradation of apoptosis inhibitors (Doherty & Baehrecke, 2018;Nikoletopoulou et al, 2013). When apoptosis is triggered, there is a caspasemediated cleavage of essential proteins for autophagy (Kang et al, 2011;Sever & Demir, 2017). Among the caspases, Caspase-3 (Casp3) is a key effector molecule of the apoptotic program, which is responsible for the proteolytic cleavage of a wide range of cellular proteins that lead to the characteristic morphological changes of apoptosis (Huettenbrenner et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Autophagy and Cathepsin D mediated apoptosis contributing to ovarian follicular atresia in the Nile tilapia

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Melo

Pinheiro

et al. 2019

Molecular Reproduction Devel

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Follicular atresia is a hormonally controlled degenerative process involving apoptosis of the somatic and germ cells. Since different signaling pathways can induce cell death, the aim of the present study was to investigate cell death signaling and crosstalk between autophagic, apoptotic, and lysosomal proteins during follicular atresia in Nile tilapia. For this, females were kept in controlled conditions for 21 days, and ovary samples were collected weekly. The atretic follicles (AF) were analyzed in three regression phases: Early, advanced, and late. Under electron microscopy, the follicular cells exhibited numerous protein synthesis organelles in the early AF. Immunoreactivity for Bcl2, Beclin1, Lc3, and Cathepsin D increased significantly in advanced AF (p < .001), when follicular cells were in intense yolk phagocytosis. In this phase, autophagosomes and autolysosomes were frequently observed. In the late AF, follicular cells had a markedly electron‐lucid cytoplasm and immunoreactivity for Bax and TUNEL assay indicated an elevated apoptosis rate. Colocalisation of Lamp1/Cathepsin D and Lc3/Caspase‐3 suggests dynamic crosstalk between the autophagy, apoptosis, and lysosome pathways. Taken together, the data indicate that autophagy plays a role in the homeostasis and clearance of the follicular cells preceding Cathepsin D mediated apoptosis during follicular atresia in Nile tilapia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Autophagy and Cathepsin D mediated apoptosis contributing to ovarian follicular atresia in the Nile tilapia

Sales

Melo

Pinheiro

et al. 2019

Molecular Reproduction Devel

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“…Autophagy, another cell death pathway that is important in tumor biology, was also investigated in SKOV3 cells following treatment with 15d-PGJ 2 and its derivatives. The inhibition of autophagy was suggested to allow the continued growth of pre-cancerous cells and autophagy may act as a tumor suppressor ( 34 , 35 ). Generally, cancer cells require autophagy to survive nutrient-limiting and low-oxygen conditions, particularly in the poorly vascularized internal region of the tumor.…”

Section: Discussionmentioning

confidence: 99%

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

et al. 2018

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Clinically relevant sirtuin (SIRT) inhibitors may possess antitumor activities. A previous study indicated that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) exhibited potent anticancer activity by SIRT1 inhibition. Therefore, the aim of the present study was to investigate whether its derivatives (J11-C1 and J19) exhibited anticancer activity against ovarian cancer SKOV3 cells. Cell viability was determined using an MTT assay. Cell cycle arrest, apoptosis and autophagy were determined using flow cytometry or western blot analysis. J11-Cl and J19 were less cytotoxic to SKOV3 cells compared with 15d-PGJ2. Molecular docking studies supported the interactions of 15d-PGJ2, J11-Cl and J19 with various amino acids in SIRT1 proteins. Similar to 15d-PGJ2, J11-C1 and J19 inhibited SIRT1 enzymatic activity and decreased SIRT1 expression levels in a concentration-dependent manner. J11-C1 induced apoptotic cell death more effectively compared with J19, which was associated with markedly decreased expression of the anti-apoptotic molecule B-cell lymphoma 2 (Bcl-2). Furthermore, the levels of light chain 3-II (LC3-II) and beclin-1 were clearly induced in SKOV3 cells treated with J11-Cl. Thus, 15d-PGJ2 and its derivatives exhibited anticancer activity possibly by inducing apoptotic or autophagic cell death pathways. Collectively, the results of the present study suggest that 15d-PGJ2 and its derivatives exerted antitumor activity by selectively modulating the expression of genes associated with cell cycle arrest, apoptosis and autophagy. Notably, J11-C1 is a novel candidate SIRT1 inhibitor with anticancer activity.

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“…Constitutive autophagy occurs at basal levels and regulates cellular homeostasis, while activated autophagy promotes cell health and survival in response to stressful conditions as starvation, inflammation, hypoxia, and oxidative stress [20][21][22], or paradoxically, it contributes to aggravate cell damage [23][24][25]. In many neurological pathologies, such as cerebral ischemia [26], traumatic brain injury [27,28], and epilepsy [29], autophagy is involved in neuronal injury, but its role is controversial.…”

Section: Introductionmentioning

confidence: 99%

Autophagy is Activated In Vivo during Trimethyltin-Induced Apoptotic Neurodegeneration: A Study in the Rat Hippocampus

Ceccariglia

Alvino

et al. 2019

IJMS

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Trimethyltin (TMT) is an organotin compound known to produce significant and selective neuronal degeneration and reactive astrogliosis in the rodent central nervous system. Autophagy is the main cellular mechanism for degrading and recycling protein aggregates and damaged organelles, which in different stress conditions, such as starvation, generally improves cell survival. Autophagy is documented in several pathologic conditions, including neurodegenerative diseases. This study aimed to investigate the autophagy and apoptosis signaling pathways in hippocampal neurons of TMT-treated (Wistar) rats to explore molecular mechanisms involved in toxicant-induced neuronal injury. The microtubule-associated protein light chain (LC3, autophagosome marker) and sequestosome1 (SQSTM1/p62) (substrate of autophagy-mediated degradation) expressions were examined by Western blotting at different time points after intoxication. The results demonstrate that the LC3 II/I ratio significantly increased at 3 and 5 days, and that p62 levels significantly decreased at 7 and 14 days. Immunofluorescence images of LC3/neuronal nuclear antigen (NeuN) showed numerous strongly positive LC3 neurons throughout the hippocampus at 3 and 5 days. The terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL) assay indicated an increase in apoptotic cells starting from 5 days after treatment. In order to clarify apoptotic pathway, immunofluorescence images of apoptosis-inducing factor (AIF)/NeuN did not show nuclear translocation of AIF in neurons. Increased expression of cleaved Caspase-3 was revealed at 5–14 days in all hippocampal regions by Western blotting and immunohistochemistry analyses. These data clearly demonstrate that TMT intoxication induces a marked increase in both autophagy and caspase-dependent apoptosis, and that autophagy occurring just before apoptosis could have a potential role in neuronal loss in this experimental model of neurodegeneration.

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Autophagy: Cell death or survive mechanism

Cited by 17 publications

References 55 publications

Autophagy and Cathepsin D mediated apoptosis contributing to ovarian follicular atresia in the Nile tilapia

Autophagy and Cathepsin D mediated apoptosis contributing to ovarian follicular atresia in the Nile tilapia

Novel SIRT1 inhibitor 15-deoxy-Δ12,14-prostaglandin J2 and its derivatives exhibit anticancer activity through apoptotic or autophagic cell death pathways in SKOV3 cells

Autophagy is Activated In Vivo during Trimethyltin-Induced Apoptotic Neurodegeneration: A Study in the Rat Hippocampus

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