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Stress Signaling and Programmed Cell Death

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (1 May 2023) | Viewed by 24672

Special Issue Editor

Special Issue Information

Dear Colleagues, 

Organisms are continuously exposed to various types of stress from external and internal environments. In order to protect cells against such stresses, each cell is equipped with multiple signal transduction systems that elicit a wide range of cellular responses to adapt to or resist such stresses. These signal transduction systems are often described as “stress signaling”. Compelling evidence indicates that the dysregulation of stress signaling induces aberrant responses to stresses, which is responsible for various diseases. Programmed cell death (PCD) is perceived as a crucial event during development and tissue formation. As a stress response, PCD also plays a critical role in the elimination of cells suffering severe stress-induced damage to maintain homeostasis within multicellular organisms, and a number of stress signaling pathways are involved in the regulation of PCD. In this Special Issue, studies of novel signaling mechanisms and pathological processes associated with PCD are welcome.

Dr. Takuya Noguchi
Guest Editor

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Keywords

  • apoptosis
  • non-apoptotic cell death
  • inflammatory cell death
  • cancer
  • neurodegenerative disease

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Published Papers (12 papers)

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Research

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16 pages, 3297 KiB  
Article
Anti-Inflammatory and Antioxidant Properties of Squalene in Copper Sulfate-Induced Inflammation in Zebrafish (Danio rerio)
by Peng Zhang, Naicheng Liu, Mingyang Xue, Mengjie Zhang, Zidong Xiao, Chen Xu, Yuding Fan, Wei Liu, Junqiang Qiu, Qinghua Zhang and Yong Zhou
Int. J. Mol. Sci. 2023, 24(10), 8518; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108518 - 10 May 2023
Cited by 3 | Viewed by 1985
Abstract
Long-term or excessive oxidative stress can cause serious damage to fish. Squalene can be added to feed as an antioxidant to improve the body constitution of fish. In this study, the antioxidant activity was detected by 2,2-diphenyl-1-acrylhydrazyl (DPPH) test and fluorescent probe (dichloro-dihydro-fluorescein [...] Read more.
Long-term or excessive oxidative stress can cause serious damage to fish. Squalene can be added to feed as an antioxidant to improve the body constitution of fish. In this study, the antioxidant activity was detected by 2,2-diphenyl-1-acrylhydrazyl (DPPH) test and fluorescent probe (dichloro-dihydro-fluorescein diacetate). Transgenic Tg (lyz: DsRed2) zebrafish were used to evaluate the effect of squalene on CuSO4-induced inflammatory response. Quantitative real-time reverse transcription polymerase chain reaction was used to examine the expression of immune-related genes. The DPPH assay demonstrated that the highest free radical scavenging exerted by squalene was 32%. The fluorescence intensity of reactive oxygen species (ROS) decreased significantly after 0.7% or 1% squalene treatment, and squalene could exert an antioxidative effect in vivo. The number of migratory neutrophils in vivo was significantly reduced after treatment with different doses of squalene. Moreover, compared with CuSO4 treatment alone, treatment with 1% squalene upregulated the expression of sod by 2.5-foldand gpx4b by 1.3-fold to protect zebrafish larvae against CuSO4-induced oxidative damage. Moreover, treatment with 1% squalene significantly downregulated the expression of tnfa and cox2. This study showed that squalene has potential as an aquafeed additive to provide both anti-inflammatory and antioxidative properties. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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13 pages, 3551 KiB  
Article
Distinct Signaling Pathways for Autophagy-Driven Cell Death and Survival in Adult Hippocampal Neural Stem Cells
by Seol-Hwa Jeong, Hyun-Kyu An, Shinwon Ha and Seong-Woon Yu
Int. J. Mol. Sci. 2023, 24(9), 8289; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24098289 - 05 May 2023
Cited by 1 | Viewed by 1236
Abstract
Autophagy is a cellular catabolic process that degrades and recycles cellular materials. Autophagy is considered to be beneficial to the cell and organism by preventing the accumulation of toxic protein aggregates, removing damaged organelles, and providing bioenergetic substrates that are necessary for survival. [...] Read more.
Autophagy is a cellular catabolic process that degrades and recycles cellular materials. Autophagy is considered to be beneficial to the cell and organism by preventing the accumulation of toxic protein aggregates, removing damaged organelles, and providing bioenergetic substrates that are necessary for survival. However, autophagy can also cause cell death depending on cellular contexts. Yet, little is known about the signaling pathways that differentially regulate the opposite outcomes of autophagy. We have previously reported that insulin withdrawal (IW) or corticosterone (CORT) induces autophagic cell death (ACD) in adult hippocampal neural stem (HCN) cells. On the other hand, metabolic stresses caused by 2-deoxy-D-glucose (2DG) and glucose-low (GL) induce autophagy without death in HCN cells. Rather, we found that 2DG-induced autophagy was cytoprotective. By comparing IW and CORT conditions with 2DG treatment, we revealed that ERK and JNK are involved with 2DG-induced protective autophagy, whereas GSK-3β regulates death-inducing autophagy. These data suggest that cell death and survival-promoting autophagy undergo differential regulation with distinct signaling pathways in HCN cells. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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14 pages, 2583 KiB  
Article
Cadmium Disrupted ER Ca2+ Homeostasis by Inhibiting SERCA2 Expression and Activity to Induce Apoptosis in Renal Proximal Tubular Cells
by Kongdong Li, Chuanzhi Guo, Jiacheng Ruan, Bo Ning, Chris Kong-Chu Wong, Haifeng Shi and Jie Gu
Int. J. Mol. Sci. 2023, 24(6), 5979; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065979 - 22 Mar 2023
Cited by 3 | Viewed by 1471
Abstract
Cadmium (Cd2+) exposure induces chronic kidney disease and renal cancers, which originate from injury and cancerization of renal tubular cells. Previous studies have shown that Cd2+ induced cytotoxicity by disrupting the intracellular Ca2+ homeostasis that is physically regulated by [...] Read more.
Cadmium (Cd2+) exposure induces chronic kidney disease and renal cancers, which originate from injury and cancerization of renal tubular cells. Previous studies have shown that Cd2+ induced cytotoxicity by disrupting the intracellular Ca2+ homeostasis that is physically regulated by the endoplasmic reticulum (ER) Ca2+ store. However, the molecular mechanism of ER Ca2+ homeostasis in Cd2+-induced nephrotoxicity remains unclear. In this study, our results firstly revealed that the activation of calcium-sensing receptor (CaSR) by NPS R-467 could protect against Cd2+ exposure-induced cytotoxicity of mouse renal tubular cells (mRTEC) by restoring ER Ca2+ homeostasis through the ER Ca2+ reuptake channel sarco/endoplasmic reticulum Ca2+-ATPase (SERCA). Cd2+-induced ER stress and cell apoptosis were effectively abrogated by SERCA agonist CDN1163 and SERCA2 overexpression. In addition, in vivo, and in vitro results proved that Cd2+ reduced the expressions of SERCA2 and its activity regulator phosphorylation phospholamban (p-PLB) in renal tubular cells. Cd2+-induced SERCA2 degradation was suppressed by the treatment of proteasome inhibitor MG132, which suggested that Cd2+ reduced SERCA2 protein stability by promoting the proteasomal protein degradation pathway. These results suggested that SERCA2 played pivotal roles in Cd2+-induced ER Ca2+ imbalance and stress to contribute to apoptosis of renal tubular cells, and the proteasomal pathway was involved in regulating SERCA2 stability. Our results proposed a new therapeutic approach targeting SERCA2 and associated proteasome that might protect against Cd2+-induced cytotoxicity and renal injury. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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14 pages, 2897 KiB  
Article
Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells
by Kentaro Oh-hashi, Hibiki Nakamura, Hirotaka Ogawa, Yoko Hirata and Kaori Sakurai
Int. J. Mol. Sci. 2023, 24(6), 5787; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24065787 - 17 Mar 2023
Cited by 2 | Viewed by 1538
Abstract
OSW-1, a steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, is a promising compound for an anticancer drug; however, its cytotoxic mechanisms have not been fully elucidated. Therefore, we analyzed the stress responses triggered by OSW-1 in the mouse neuroblastoma cell line [...] Read more.
OSW-1, a steroidal saponin isolated from the bulbs of Ornithogalum saundersiae, is a promising compound for an anticancer drug; however, its cytotoxic mechanisms have not been fully elucidated. Therefore, we analyzed the stress responses triggered by OSW-1 in the mouse neuroblastoma cell line Neuro2a by comparing it with brefeldin A (BFA), a Golgi apparatus-disrupting reagent. Among the Golgi stress sensors TFE3/TFEB and CREB3, OSW-1 induced dephosphorylation of TFE3/TFEB but not cleavage of CREB3, and induction of the ER stress-inducible genes GADD153 and GADD34 was slight. On the other hand, the induction of LC3-II, an autophagy marker, was more pronounced than the BFA stimulation. To elucidate OSW-1-induced gene expression, we performed a comprehensive gene analysis using a microarray method and observed changes in numerous genes involved in lipid metabolism, such as cholesterol, and in the regulation of the ER–Golgi apparatus. Abnormalities in ER–Golgi transport were also evident in the examination of secretory activity using NanoLuc-tag genes. Finally, we established Neuro2a cells lacking oxysterol-binding protein (OSBP), which were severely reduced by OSW-1, but found OSBP deficiency had little effect on OSW-1-induced cell death and the LC3-II/LC3-I ratio in Neuro2a cells. Future work to elucidate the relationship between OSW-1-induced atypical Golgi stress responses and autophagy induction may lead to the development of new anticancer agents. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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15 pages, 3871 KiB  
Article
Delayed TBI-Induced Neuronal Death in the Ipsilateral Hippocampus and Behavioral Deficits in Rats: Influence of Corticosterone-Dependent Survivorship Bias?
by Ilia Komoltsev, Daria Shalneva, Olga Kostyunina, Aleksandra Volkova, Stepan Frankevich, Natalia Shirobokova, Anastasia Belikova, Sofia Balan, Olesya Chizhova, Olga Salyp, Daria Bashkatova, Pavel Kostrukov, Aleksandra Soloveva, Margarita Novikova and Natalia Gulyaeva
Int. J. Mol. Sci. 2023, 24(5), 4542; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054542 - 25 Feb 2023
Cited by 3 | Viewed by 1608
Abstract
Acute and chronic corticosterone (CS) elevations after traumatic brain injury (TBI) may be involved in distant hippocampal damage and the development of late posttraumatic behavioral pathology. CS-dependent behavioral and morphological changes were studied 3 months after TBI induced by lateral fluid percussion in [...] Read more.
Acute and chronic corticosterone (CS) elevations after traumatic brain injury (TBI) may be involved in distant hippocampal damage and the development of late posttraumatic behavioral pathology. CS-dependent behavioral and morphological changes were studied 3 months after TBI induced by lateral fluid percussion in 51 male Sprague–Dawley rats. CS was measured in the background 3 and 7 days and 1, 2 and 3 months after TBI. Tests including open field, elevated plus maze, object location, new object recognition tests (NORT) and Barnes maze with reversal learning were used to assess behavioral changes in acute and late TBI periods. The elevation of CS on day 3 after TBI was accompanied by early CS-dependent objective memory impairments detected in NORT. Blood CS levels > 860 nmol/L predicted delayed mortality with an accuracy of 0.947. Ipsilateral neuronal loss in the hippocampal dentate gyrus, microgliosis in the contralateral dentate gyrus and bilateral thinning of hippocampal cell layers as well as delayed spatial memory deficits in the Barnes maze were revealed 3 months after TBI. Because only animals with moderate but not severe posttraumatic CS elevation survived, we suggest that moderate late posttraumatic morphological and behavioral deficits may be at least partially masked by CS-dependent survivorship bias. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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21 pages, 6075 KiB  
Article
1α,25(OH)2D3 Promotes the Autophagy of Porcine Ovarian Granulosa Cells as a Protective Mechanism against ROS through the BNIP3/PINK1 Pathway
by Shiyou Wang, Qichun Yao, Fan Zhao, Wenfei Cui, Christopher A. Price, Yifan Wang, Jing Lv, Hong Tang and Zhongliang Jiang
Int. J. Mol. Sci. 2023, 24(5), 4364; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054364 - 22 Feb 2023
Viewed by 1125
Abstract
Vitamin D (VD) is one of the important nutrients required by livestock; however, VD deficiency is reported to be widespread. Earlier studies have suggested a potential role for VD in reproduction. Studies on the correlation between VD and sow reproduction are limited. The [...] Read more.
Vitamin D (VD) is one of the important nutrients required by livestock; however, VD deficiency is reported to be widespread. Earlier studies have suggested a potential role for VD in reproduction. Studies on the correlation between VD and sow reproduction are limited. The aim of the current study was aimed to determine the role of 1,25-dihydroxy vitamin D3 (1α,25(OH)2D3) on porcine ovarian granulosa cells (PGCs) in vitro to provide a theoretical basis for improving the reproductive efficiency of sows. We used chloroquine (autophagy inhibitor) and reactive oxygen species (ROS) scavenger N-acetylcysteine in conjunction with 1α,25(OH)2D3 to explore the effect on PGCs. The results showed that 10 nM of 1α,25(OH)2D3 increased PGC viability and ROS content. In addition, 1α,25(OH)2D3 induces PGC autophagy according to the gene transcription and protein expression levels of LC3, ATG7, BECN1, and SQSTM1 and promotes the generation of autophagosomes. 1α,25(OH)2D3-induced autophagy affects the synthesis of E2 and P4 in PGCs. We investigated the relationship between ROS and autophagy, and the results showed that 1α,25(OH)2D3-induced ROS promoted PGC autophagy. The ROS-BNIP3-PINK1 pathway was involved in PGC autophagy induced by 1α,25(OH)2D3. In conclusion, this study suggests that 1α,25(OH)2D3 promotes PGC autophagy as a protective mechanism against ROS via the BNIP3/PINK1 pathway. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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16 pages, 2757 KiB  
Article
Asprosin Exerts Pro-Inflammatory Effects in THP-1 Macrophages Mediated via the Toll-like Receptor 4 (TLR4) Pathway
by Kiran Shabir, Seley Gharanei, Sophie Orton, Vanlata Patel, Parbata Chauhan, Emmanouil Karteris, Harpal S. Randeva, James E. Brown and Ioannis Kyrou
Int. J. Mol. Sci. 2023, 24(1), 227; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24010227 - 23 Dec 2022
Cited by 8 | Viewed by 2402
Abstract
Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. [...] Read more.
Adipose tissue is a dynamic endocrine organ, secreting a plethora of adipokines which play a key role in regulating metabolic homeostasis and other physiological processes. An altered adipokine secretion profile from adipose tissue depots has been associated with obesity and related cardio-metabolic diseases. Asprosin is a recently described adipokine that is released in response to fasting and can elicit orexigenic and glucogenic effects. Circulating asprosin levels are elevated in a number of cardio-metabolic diseases, including obesity and type 2 diabetes. In vitro studies have reported pro-inflammatory effects of asprosin in a variety of tissues. The present study aimed to further elucidate the role of asprosin in inflammation by exploring its potential effect(s) in THP-1 macrophages. THP-1 monocytes were differentiated to macrophages by 48 h treatment with dihydroxyvitamin D3. Macrophages were treated with 100 nM recombinant human asprosin, 100 ng/mL lipopolysaccharide (LPS), and 10 μM caffeic acid phenethyl ester (CAPE; an inhibitor of NFκB activation) or 1 µM TAK-242 (a Toll-like receptor 4, TLR4, inhibitor). The expression and secretion of pertinent pro-inflammatory mediators were measured by qPCR, Western blot, ELISA and Bioplex. Asprosin stimulation significantly upregulated the expression and secretion of the pro-inflammatory cytokines: tumour necrosis factor α (TNFα), interleukin-1β (IL-1β), IL-8 and IL-12 in vitro. This pro-inflammatory response in THP-1 macrophages was partly attenuated by the treatments with CAPE and was significantly inhibited by TAK-242 treatment. Asprosin-induced inflammation is significantly counteracted by TLR4 inhibition in THP-1 macrophages, suggesting that asprosin exerts its pro-inflammatory effects, at least in part, via the TLR4 signalling pathway. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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18 pages, 5577 KiB  
Article
Antitumor Effect of Cycloastragenol in Colon Cancer Cells via p53 Activation
by Doil Park, Ji Hoon Jung, Hyun Min Ko, Wona Jee, Hyungsuk Kim and Hyeung-Jin Jang
Int. J. Mol. Sci. 2022, 23(23), 15213; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315213 - 02 Dec 2022
Cited by 2 | Viewed by 1536
Abstract
Colorectal cancer cell (CRC) is the fourth most common cancer in the world. There are several chemotherapy drugs available for its treatment, though they have side effects. Cycloastragenol (CY) is a compound from Astragalus membranaceus (Fisch.) Bge known to be effective in aging, [...] Read more.
Colorectal cancer cell (CRC) is the fourth most common cancer in the world. There are several chemotherapy drugs available for its treatment, though they have side effects. Cycloastragenol (CY) is a compound from Astragalus membranaceus (Fisch.) Bge known to be effective in aging, anti-inflammatory, anticancer, and anti-heart failure treatments. Although many studies have demonstrated the functions of CY in cancer cells, no studies have shown the effects of p53 in colon cancer cells. In this study, we found that CY reduces the viability of colon cancer cells in p53 wild-type cells compared to p53 null cells and HT29. Furthermore, CY induces apoptosis by p53 activation in a dose- and time-dependent manner. And it was confirmed that it affects the L5 gene related to p53. Additionally, CY enhanced p53 expression compared to when either doxorubicin or 5-FU was used alone. Altogether, our findings suggest that CY induces apoptosis via p53 activation and inhibits the proliferation of colon cancer cells. In addition, apoptosis occurs in colon cancer cells due to other factors. Moreover, CY is expected to have a combined effect when used together with existing treatments for colon cancer in the future. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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22 pages, 2655 KiB  
Article
The Stress Response of the Holothurian Central Nervous System: A Transcriptomic Analysis
by Sebastián Cruz-González, Eduardo Quesada-Díaz, Yamil Miranda-Negrón, Raúl García-Rosario, Humberto Ortiz-Zuazaga and José E. García-Arrarás
Int. J. Mol. Sci. 2022, 23(21), 13393; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113393 - 02 Nov 2022
Cited by 1 | Viewed by 1526
Abstract
Injury to the central nervous system (CNS) results in permanent damage and lack of function in most vertebrate animals, due to their limited regenerative capacities. In contrast, echinoderms can fully regenerate their radial nerve cord (RNC) following transection, with little to no scarring. [...] Read more.
Injury to the central nervous system (CNS) results in permanent damage and lack of function in most vertebrate animals, due to their limited regenerative capacities. In contrast, echinoderms can fully regenerate their radial nerve cord (RNC) following transection, with little to no scarring. Investigators have associated the regenerative capacity of some organisms to the stress response and inflammation produced by the injury. Here, we explore the gene activation profile of the stressed holothurian CNS. To do this, we performed RNA sequencing on isolated RNC explants submitted to the stress of transection and enzyme dissection and compared them with explants kept in culture for 3 days following dissection. We describe stress-associated genes, including members of heat-shock families, ubiquitin-related pathways, transposons, and apoptosis that were differentially expressed. Surprisingly, the stress response does not induce apoptosis in this system. Other genes associated with stress in other animal models, such as hero proteins and those associated with the integrated stress response, were not found to be differentially expressed either. Our results provide a new viewpoint on the stress response in the nervous system of an organism with amazing regenerative capacities. This is the first step in deciphering the molecular processes that allow echinoderms to undergo fully functional CNS regeneration, and also provides a comparative view of the stress response in other organisms. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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14 pages, 2727 KiB  
Article
The Distinct Roles of LKB1 and AMPK in p53-Dependent Apoptosis Induced by Cisplatin
by Tatsuya Shimada, Yohsuke Yabuki, Takuya Noguchi, Mei Tsuchida, Ryuto Komatsu, Shuhei Hamano, Mayuka Yamada, Yusuke Ezaki, Yusuke Hirata and Atsushi Matsuzawa
Int. J. Mol. Sci. 2022, 23(17), 10064; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710064 - 02 Sep 2022
Cited by 8 | Viewed by 2467
Abstract
Liver kinase B1 (LKB1) is a serine/threonine protein kinase that acts as a key tumor suppressor protein by activating its downstream kinases, such as AMP-activated protein kinase (AMPK). However, the regulatory actions of LKB1 and AMPK on DNA damage response (DDR) remain to [...] Read more.
Liver kinase B1 (LKB1) is a serine/threonine protein kinase that acts as a key tumor suppressor protein by activating its downstream kinases, such as AMP-activated protein kinase (AMPK). However, the regulatory actions of LKB1 and AMPK on DNA damage response (DDR) remain to be explored. In this study, we investigated the function of LKB1 in DDR induced by cisplatin, a representative DNA-damaging agent, and found that LKB1 stabilizes and activates p53 through the c-Jun N-terminal kinase (JNK) pathway, which promotes cisplatin-induced apoptosis in human fibrosarcoma cell line HT1080. On the other hand, we found that AMPKα1 and α2 double knockout (DKO) cells showed enhanced stabilization of p53 and increased susceptibility to apoptosis induced by cisplatin, suggesting that AMPK negatively regulates cisplatin-induced apoptosis. Moreover, the additional stabilization of p53 and subsequent apoptosis in AMPK DKO cells were clearly canceled by the treatment with the antioxidants, raising the possibility that AMPK suppresses the p53 activation mediated by oxidative stress. Thus, our findings unexpectedly demonstrate the reciprocal regulation of p53 by LKB1 and AMPK in DDR, which provides insights into the molecular mechanisms of DDR. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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Review

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15 pages, 1333 KiB  
Review
Regulation of Oocyte Apoptosis: A View from Gene Knockout Mice
by Sandeep Kaur and Manabu Kurokawa
Int. J. Mol. Sci. 2023, 24(2), 1345; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021345 - 10 Jan 2023
Cited by 3 | Viewed by 2649
Abstract
Apoptosis is a form of programmed cell death that plays a critical role in cellular homeostasis and development, including in the ovarian reserve. In humans, hundreds of thousands of oocytes are produced in the fetal ovary. However, the majority die by apoptosis before [...] Read more.
Apoptosis is a form of programmed cell death that plays a critical role in cellular homeostasis and development, including in the ovarian reserve. In humans, hundreds of thousands of oocytes are produced in the fetal ovary. However, the majority die by apoptosis before birth. After puberty, primordial follicles develop into mature follicles. While only a large dominant follicle is selected to ovulate, smaller ones undergo apoptosis. Despite numerous studies, the mechanism of oocyte death at the molecular level remains elusive. Over the last two and a half decades, many knockout mouse models disrupting key genes in the apoptosis pathway have been generated. In this review, we highlight some of the phenotypes and discuss distinct and overlapping roles of the apoptosis regulators in oocyte death and survival. We also review how the transcription factor p63 and its family members may trigger oocyte apoptosis in response to DNA damage. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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30 pages, 2312 KiB  
Review
Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death
by Adalberto Merighi and Laura Lossi
Int. J. Mol. Sci. 2022, 23(23), 15186; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315186 - 02 Dec 2022
Cited by 12 | Viewed by 3272
Abstract
Besides protein processing, the endoplasmic reticulum (ER) has several other functions such as lipid synthesis, the transfer of molecules to other cellular compartments, and the regulation of Ca2+ homeostasis. Before leaving the organelle, proteins must be folded and post-translationally modified. Protein folding [...] Read more.
Besides protein processing, the endoplasmic reticulum (ER) has several other functions such as lipid synthesis, the transfer of molecules to other cellular compartments, and the regulation of Ca2+ homeostasis. Before leaving the organelle, proteins must be folded and post-translationally modified. Protein folding and revision require molecular chaperones and a favorable ER environment. When in stressful situations, ER luminal conditions or chaperone capacity are altered, and the cell activates signaling cascades to restore a favorable folding environment triggering the so-called unfolded protein response (UPR) that can lead to autophagy to preserve cell integrity. However, when the UPR is disrupted or insufficient, cell death occurs. This review examines the links between UPR signaling, cell-protective responses, and death following ER stress with a particular focus on those mechanisms that operate in neurons. Full article
(This article belongs to the Special Issue Stress Signaling and Programmed Cell Death)
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