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1.
To date, our knowledge of apoptosis regulation in insects comes almost exclusively from the model organism Drosophila melanogaster. In contrast, despite the identification of numerous genes that are presumed to regulate apoptosis in other insects based
on sequence homology, little has been done to examine the molecular pathways that regulate apoptosis in other insects, including
medically important disease vectors. In D. melanogaster, the core apoptosis pathway consists of the caspase negative regulator DIAP1, IAP antagonists, the initiator caspase Dronc
and its activating protein Ark, and the effector caspase DrICE. Here we have studied the functions of several genes from the
mosquito disease vector Aedes aegypti that share homology with the core apoptosis genes in D. melanogaster. Silencing of the iap1 gene in the A. aegypti cell line Aag2 caused spontaneous apoptosis, indicating that IAP1 plays a role in cell survival similar to that of DIAP1.
Silencing A. aegypti ark or dronc completely inhibited apoptosis triggered by several different apoptotic stimuli. However, individual silencing of the effector
caspases CASPS7 or CASPS8, which are the closest relatives to DrICE, only partially inhibited apoptosis, and silencing both
CASPS7 and CASPS8 together did not have a significant additional effect. Our results suggest that the core pathway that regulates
apoptosis in A. aegypti is similar to that of D. melanogaster, but that more than one effector caspase is involved in apoptosis in A. aegypti. This is interesting in light of the fact that the caspase family has expanded in mosquitoes compared to D. melanogaster. 相似文献
2.
The strain distribution pattern of susceptibility to thymocyte apoptosis induced by ionizing radiation in 20 CcS/Dem recombinant congenic (RC) strains derived from the strains BALB/cHeA (susceptible) and STS/A (resistant) indicates that this trait is controlled by several genes. Recently, we mapped a novel apoptosis susceptibility gene Rapop1 (radiation-induced apoptosis 1) to chromosome 16 (N. Mori et al., 1995, Genomics 25: 604-614). In the present study, the analysis of F2 crosses between the resistant RC strain CcS-8 and the susceptible strain BALB/cHeA or the highly susceptible RC strain CcS-10 demonstrated two additional apoptosis susceptibility genes, Rapop2 and Rapop3, located in the proximal region of chromosome 9 and the telomeric region of chromosome 3, respectively. The possible candidate genes for these loci are discussed. 相似文献
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Schetelig MF Nirmala X Handler AM 《Apoptosis : an international journal on programmed cell death》2011,16(8):759-768
Pro-apoptotic proteins from the reaper, hid, grim (RHG) family are primary regulators of programmed cell death in Drosophila due to their antagonistic effect on inhibitor of apoptosis (IAP) proteins, thereby releasing IAP-inhibition of caspases that
effect apoptosis. Using a degenerate PCR approach to conserved domains from the 12 Drosophila species, we have identified the first reaper and hid orthologs from a tephritid, the Caribfly Anastrepha
suspensa. As-hid is the first identified non-drosophilid homolog of hid, and As-rpr is the second non-drosophilid rpr homolog. Both genes share more than 50% amino acid sequence identity with their Drosophila homologs, suggesting that insect pro-apoptotic peptides may be more conserved than previously anticipated. Importantly, both
genes encode the conserved IBM and GH3 motifs that are key for IAP-inhibition and mitochondrial localization. Functional verification
of both genes as cell death effectors was demonstrated by cell death assays in A. suspensa embryonic cell culture, as well as in heterologous Drosophila melanogaster S2 cells. Notably, heterologous cell death activity was found to be higher for Anastrepha genes than their Drosophila counterparts. In common with the Drosophila cognates, As-hid and As-rpr negatively regulated the Drosophila inhibitor of apoptosis (DIAP1) gene to promote apoptosis, and both genes when used together effected increased cell death
activity, indicating a co-operative function for As-hid and As-rpr. We show that these tephritid cell death genes are functional and potent as cell death effectors, and could be used to design
improved transgenic lethality systems for insect population control. 相似文献
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Peng Chen Tao‐Tao Kang Xi‐Yan Bao Zhan‐Qi Dong Yan Zhu Wen‐Fu Xiao Min‐Hui Pan Cheng Lu 《Insect Science》2020,27(3):463-474
As an important insect immune response, apoptosis plays a critical role in the interaction between baculoviruses and insect hosts. Previous reports have identified inhibitor of apoptosis (IAP) proteins in both insects and baculoviruses, but the relationship between these proteins is still not clearly understood. Here, we found that insect IAP proteins were clustered with baculovirus IAP3, suggesting that the baculovirus iap3 gene might be derived from the Lepidoptera or Diptera. We demonstrated that Bombyx mori inhibitor of apoptosis (Bmiap) gene had an inhibitory effect on apoptosis in silkworm cells. Further analysis of the effects of Bmiap genes on the proliferation of B. mori nucleopolyhedrovirus (BmNPV) showed that both the Bmiap and BmNPV iap genes increased BmNPV proliferation after BmNPV infected silkworm cells. Our results also indicated that BmNPV IAP1 and IAP2 directly interacted with BmIAP in silkworm cells, implying that the Bmiap gene might be hijacked by BmNPV iap genes during BmNPV infection. Taken together, our results provide important insights into the functional relationships of iap genes, and improve our knowledge of apoptosis in baculoviruses and insect hosts. 相似文献
8.
Background
Virulent Mycobacterium leprae interfere with host defense mechanisms such as cytokine activation and apoptosis. The mitochondrial pathway of apoptosis is regulated by the Bcl-2 family of proteins. Expression of Fas ligand and apoptotic proteins is found in leprosy lesions and M. leprae has been shown to activate pro-apoptotic Bcl-2 genes, Bak and Bax. However, the mechanism by which M. leprae modulates apoptosis is as yet unclear. We investigated expression of apoptotic genes in THP-1 monocytes in response to infection by M. leprae and non-pathogenic M. bovis BCG. 相似文献9.
Hsiao-Ling Huang Chung-Ken Wu Dai-Jia Wu Wen-Hsiu Liu Ying-Shiung Lee Chi-Ling Wu 《The journal of gene medicine》2023,25(11):e3555
Background
Osteoporosis is a disease of the bone system that causes a decrease in skeletal density and degrades skeletal tissue. Decreased bone quality, so that bones are easily broken, damaged and fractured, is an important public health problem. Previous studies have shown that the maintenance of adult bone mass is not only due to changes in bone marrow and bone cells. By regulating apoptosis, they change the lifespan of each individual. This study influences understanding of the function of apoptosis in the pathogenesis of osteoporosis and the importance of controlling the mechanisms of osteoporosis.Methods
On the National Institute of Biotechnology Information website, Gene Expression Omnibus (GEO) microarray data and GSE551495 GEO profiles were collected. The gene set enrichment analysis tool was used to confirm the enrichment of genetic sets in relation to the gene set. The collection of C2 gene sets is compiled from the KEGG ( https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://www.kegg.jp/kegg/ ) online database and REACTOME ( https://www.gsea-msigdb.org/gsea/msigdb/human/search.jsp and https://reactome.org/ ) pathway analysis. The Search Tool for the Retrieval of Interaction Genes (STRING) website was used to construct and select proteins and genes. The comparative toxicological genomic database (CTD) tools can be used to predict the relationship between apoptosis, osteoporosis-related genes and interactions between central genes and osteoporosis.Results
These results generally expand our understanding of the path of apoptosis in osteoporosis. We have discovered genes CASP9, CASP8, CASP3, BAX and TP53 associated with osteoporosis. In activation of KEGG apoptosis and REACTOME, caspase activation through the extrinsic apoptotic signaling pathway is characterized by the identification of a subcollection of C2. Other STRINGs show the formation of protein networks and central gene selection, and CTD can accurately predict the relationship between these apoptosis pathways and central genes.Conclusions
Our research has highlighted the importance of the osteoporosis pathway associated with osteoporosis apoptosis with several analytical approaches. These results have broadened our understanding of the pathways of osteoporosis apoptosis. It is particularly possible to predict the sensitivity and vulnerability to osteoporosis. 相似文献10.
Apoptosis Mediated by a Novel Leucine Zipper Protein Par-4 总被引:4,自引:0,他引:4
The prostate apoptosis response-4 (par-4) gene was isolated in a differential screen for immediate-early genes that are up-regulated during apoptosis of prostate cancer cells. Unlike most other immediate-early genes, par-4 is exclusively induced during apoptosis. The expression or induction of par-4 is not restricted to prostatic cells. The par-4 gene is widely expressed in diverse normal tissues and cell types and conserved during evolution. Par-4 protein contains a leucine zipper domain that is essential for sensitization of cells to apoptosis. Functional studies indicate that par-4 expression is necessary to induce apoptosis. Par-4 protein may induce apoptosis by a p53-independent pathway that involves cytoplasmic inactivation of atypical protein kinase C isoforms resulting in down-regulation of MAP kinase activity and an up-regulation of p38 kinase activity. However, Par-4 is detected in the cytoplasm and in the nucleus, suggesting both cytoplasmic and nuclear roles for the pro-apoptotic protein. Interestingly, Par-4 is predicted to contain a death domain homologous to that of Fas or TRADD, and may therefore trigger a death cascade analogous to that of the death domain proteins. Par-4-dependent apoptosis is abrogated by Bcl-2 and by caspase inhibitors. Identification of the components of the p53-independent apoptosis pathway induced by Par-4 may help to further elucidate the mechanism of Par-4 action. Moreover, in view of the pro-apoptotic function of Par-4, its role in diseases, such as cancer and neurogenerative disorders, whose pathophysiology involves apoptotic cell death needs further investigation. 相似文献
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Maryam Vahdat-Lasemi Sara Hosseini Vahid Jajarmi Bahram Kazemi Mohammad Salehi 《Journal of cellular physiology》2019,234(8):13858-13866
miR-224 is associated with polycystic ovary syndrome (PCOS) that is an epidemic in reproductive age women. Most studies of miR-224 have focused on in vitro analyses, whereas the in vivo effects are not widely understood. In this study, we have conducted in silico analysis and found two potential miR-224 target genes, Ptx3 and Smad4 that have roles in folliculogenesis. Because patients with PCOS have decreased numbers of follicular cells related to cell apoptosis, we also investigated two apoptotic genes, Bax and Bcl2. We used the intraovarian injection method to deliver miR-224 into a mouse model. Histological examination of the ovaries was done by fluorescent microscope. Fertilization, cleavage, and developmental competence rates were counted under a stereomicroscope and compared between the studied groups. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of miR-224 was conducted to determine the levels of the studied genes in the oocytes, cumulus cells, and blastocysts. The numbers of oocytes and fertilization rate indicated a higher apoptosis index ( p < 0.05) and increased numbers of degenerated embryos with irregular blastomeres and fragmented cytoplasm in the experimental group. RT-PCR results indicated a significant increase in miR-224 levels in the manipulated group. Of the four analyzed genes, Ptx3, Smad4, and Bcl2 had decreased levels in the transfected group, with increased Bax expression ( p < 0.05). This data showed that miR-224 negatively affected ovulation in the mouse model by decreasing Ptx3 and Smad4 expressions. The changes in Bcl2 and Bax expression levels, as apoptosis biomarkers, showed that apoptosis was a secondary outcome of the effect of miR-224. 相似文献
13.
L. B. Djansugurova 《Russian Journal of Developmental Biology》2011,42(6):376-388
Data on involvement of nitric oxide in apoptosis are contradictory. The balance between anti- and proapoptotic activities
of nitric oxide depends on many factors, including its concentration in a tissue and interactions with other regulators of
apoptosis. This paper describes the results of a series of experiments on the effect of nitric oxide donors and inhibitors
as well as dNOS1 and dNOS4 transgenes on the apoptosis on drosophila Lobe
RSV
mutant strain and wild-type strain Oregon R. It has been shown that a high nitric oxide content in cells is able to inhibit antiapoptotic effect of HSP70 and stimulate
apoptosis, possibly, via the grim-mediated apoptotic pathway. Moreover, long-term action of a high nitric oxide concentration during the entire development
more efficiently stimulates the proapoptotic genes as compared with short-term action of this agent. 相似文献
14.
Banus S Pennings J Vandebriel R Wester P Breit T Mooi F Hoebee B Kimman T 《Immunogenetics》2007,59(7):555-564
Host genetics determines the course of Bordetella pertussis infection in mice. Previously, we found four loci, Tlr4 and three novel loci, designated Bps 1–3, that are involved in the control of B. pertussis infection. The purpose of the present study was to identify candidate genes that could explain genetic differences in the
course of B. pertussis infection, assuming that such genes are differentially regulated upon infection. We, therefore, studied the course of mRNA
expression in the lungs after B. pertussis infection. Of the 22,000 genes investigated, 1,841 were significantly differentially expressed with 1,182 genes upregulated
and 659 genes downregulated. Upregulated genes were involved in immune-related processes, such as the acute-phase response,
antigen presentation, cytokine production, inflammation, and apoptosis, while downregulated genes were mainly involved in
nonimmune processes, such as development and muscle contraction. Pathway analysis revealed the involvement of granulocyte
function, toll-like receptor signaling pathway, and apoptosis. Nine of the differentially expressed genes were located in
Bps-1, 13 were located in Bps-2, and 62 were located in Bps-3. We conclude that B. pertussis infection induces a wide and complex response, which appears to be partly specific for B. pertussis and partly nonspecific. We envisage that these data will be helpful in identifying polymorphic genes that affect the susceptibility
and course of B. pertussis infection in humans.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Raw and normalized data of the experiment can be
accessed at the online database ArrayExpress http://www.ebi.ac.uk/arrayexpress/ 相似文献
15.
Vector competence and innate immune responses to dengue virus infection in selected laboratory and field‐collected Stegomyia aegypti (= Aedes aegypti)
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I. M. SERRATO P. A. CAICEDO Y. OROBIO C. LOWENBERGER C. B. OCAMPO 《Medical and veterinary entomology》2017,31(3):312-319
Control of dengue virus (DenV) transmission, primarily based on strategies to reduce populations of the principle vector Stegomya aegypti (= Aedes aegypti) (Diptera: Culicidae), is difficult to sustain over time. Other potential strategies aim to manipulate characteristics such as vector competence (VC), the innate capacity of the vector to transmit the virus. Previous studies have identified genetic factors, including differential expression of apoptosis‐related genes, associated with the refractory and susceptible phenotypes in selected strains of S. aegypti from Cali, Colombia. The present study was designed to evaluate the variability of VC in selected strains against different DenV serotypes and to determine whether field‐collected mosquitoes respond similarly to selected laboratory strains in terms of enhanced or reduced expression of apoptosis‐related genes. Vector competence differed between strains, but did not differ in response to different DenV serotypes. Differences in VC were observed among mosquitoes collected from different localities in Cali. The overexpression of the pro‐apoptosis genes, caspase 16 and Aedronc, was conserved in field‐collected refractory mosquitoes and the selected laboratory refractory strain. The results suggest that the apoptosis response is conserved among all refractory mosquitoes to inhibit the development of all DenV serotypes. 相似文献
16.
Key insight into the complexities of apoptosis may be gained from the study of its evolution in lower metazoans. In this study
we describe two genes from a cnidarian, Aiptasia pallida, that are homologous to key genes in the apoptotic pathway from vertebrates. The first is a novel ancient caspase, acasp, that displays attributes of both initiator and executioner caspases and includes a caspase recruitment domain (CARD). The
second, a Bcl-2 family member, abhp, contains a BH1 and BH2 domain and shares structural characteristics and phylogenetic affinity with a group of antiapoptotic
Bcl-2s including A1 and Bcl-2L10. The breadth of occurrence of other invertebrate homologues across the phylogenetic trees
of both genes suggests that the complexity of apoptotic pathways is an ancient trait that predates the evolution of vertebrates
and higher invertebrates such as nematodes and flies. This paves the way for establishing new lower metazoan model systems
for the study of apoptosis.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
[Reviewing Editor: Dr. Stuart Newfeld] 相似文献
17.
Ragini Kumari Kamaleshwar P. Singh James W. DuMond Jr. 《Journal of cellular biochemistry》2009,107(4):723-731
The effect of simulated microgravity on DNA damage and apoptosis is still controversial. The objective of this study was to test whether simulated microgravity conditions affect the expression of genes for DNA repair and apoptosis. To achieve this objective, human lymphocyte cells were grown in a NASA‐developed rotating wall vessel (RWV) bioreactor that simulates microgravity. The same cell line was grown in parallel under normal gravitational conditions in culture flasks. The effect of microgravity on the expression of genes was measured by quantitative real‐time PCR while DNA damage was examined by comet assay. The result of this study revealed that exposure to simulated microgravity condition decreases the expression of DNA repair genes. Mismatch repair (MMR) class of DNA repair pathway were more susceptible to microgravity condition‐induced gene expression changes than base excision repair (BER) and nucleotide excision repair (NER) class of DNA repair genes. Downregulation of genes involved in cell proliferation (CyclinD1 and PCNA) and apoptosis (Bax) was also observed. Microgravity‐induced changes in the expression of some of these genes were further verified at the protein level by Western blot analysis. The findings of this study suggest that microgravity may induce alterations in the expression of these DNA repair genes resulting in accumulation of DNA damage. Reduced expression of cell‐cycle genes suggests that microgravity may cause a reduction in cell growth. Downregulation of pro‐apoptotic genes further suggests that extended exposure to microgravity may result in a reduction in the cells' ability to undergo apoptosis. Any resistance to apoptosis seen in cells with damaged DNA may eventually lead to malignant transformation of those cells. J. Cell. Biochem. 107: 723–731, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
18.
Heat‐shock proteins 70/110 (Hsp70/110) are vital molecular chaperones and stress proteins whose expression and production are generally induced by extreme temperatures or external stresses. The Hsp70/110 family is largely conserved in diverse animals. Although many reports have studied and elaborated on the characteristics of Hsp70/110 in various species, the systematic identification and analysis of Hsp70/110 are still poor in turtles. In this study, a genomewide search was performed, and 18 candidate PsHSP70/110 family genes were identified in Chinese soft‐shelled turtle, Pelodiscus sinensis. These PsHSP70/110 proteins contained the conserved “heat shock protein 70” domain. Phylogenetic analysis of PsHSP70/110 and their homologs revealed evolutionary conservation of Hsp70/110 across different species. Tissue‐specific expression analysis showed that these PsHSP70/110 genes were differentially expressed in different tissues of P. sinensis. Furthermore, to examine the putative biological functions of PsHSP70/110, the dynamic expression of PsHSP70/110 genes was analyzed in the testis of P. sinensis during seasonal spermatogenesis following germ cell apoptosis. Notably, genes such as PsHSPA1B‐L, PsHSPA2, and PsHSPA8 were significantly upregulated in P. sinensis testes along with a seasonal decrease in apoptosis. Protein interaction prediction revealed that PsHSPA1B‐L, PsHSPA2, and PsHSPA8 may interact with each other and participate in the MAPK signaling pathway. Moreover, immunohistochemical analysis showed that PsHSPA1B‐L, PsHSPA2, and PsHSPA8 protein expression was associated with seasonal temperature variation. The expression profiling and interaction relationships of the PsHSPA1B‐L, PsHSPA2, and PsHSPA8 proteins implied their potential roles in inhibiting the apoptosis of germ cells in P. sinensis. These results provide insights into PsHSP70/110 functions and will serve as a rich resource for further investigation of HSP70/110 family genes in P. sinensis and other turtles. 相似文献
19.
Atsuko Ishizuya-Oka Takashi Hasebe Yun-Bo Shi 《Apoptosis : an international journal on programmed cell death》2010,15(3):350-364
During amphibian metamorphosis, the larval tissues/organs rapidly degenerate to adapt from the aquatic to the terrestrial
life. At the cellular level, a large quantity of apoptosis occurs in a spatiotemporally-regulated fashion in different organs
to ensure timely removal of larval organs/tissues and the development of adult ones for the survival of the individuals. Thus,
amphibian metamorphosis provides us a good opportunity to understand the mechanisms regulating apoptosis. To investigate this
process at the molecular level, a number of thyroid hormone (TH) response genes have been isolated from several organs of
Xenopus laevis tadpoles and their expression and functional analyses are now in progress using modern molecular and genetic technologies.
In this review, we will first summarize when and where apoptosis occurs in typical larva-specific and larval-to-adult remodeling
amphibian organs to highlight that the timing of apoptosis is different in different tissues/organs, even though all are induced
by the same circulating TH. Next, to discuss how TH spatiotemporally regulates the apoptosis, we will focus on apoptosis of
the X. laevis small intestine, one of the best characterized remodeling organs. Functional studies of TH response genes using transgenic
frogs and culture techniques have shown that apoptosis of larval epithelial cells can be induced by TH either cell-autonomously
or indirectly through interactions with extracellular matrix (ECM) components of the underlying basal lamina. Here, we propose
that multiple intra- and extracellular apoptotic pathways are coordinately controlled by TH to ensure massive but well-organized
apoptosis, which is essential for the proper progression of amphibian metamorphosis. 相似文献
20.
Shankar C. R. R. Chereddy Dhandapani Gurusamy Jeffrey L. Howell Subba R. Palli 《Archives of insect biochemistry and physiology》2020,104(4):e21683
RNA interference (RNAi) has become an integral part of mainstream research due to its versatility and ease of use. However, the potential nontarget effects associated with double-stranded RNAs (dsRNA) are poorly understood. To explore this, we used dsRNAs targeting the inhibitor of apoptosis (iap) gene from nine insect species and assayed their possible nontarget effects. For each assay, we used a control (dsRNA targeting the gene coding for green fluorescent protein, GFP) and a species-specific dsRNA targeting nine iap genes in insect species to evaluate target gene knockdown efficiency, apoptosis phenotype in cells and mortality in insects. Our results revealed that dsIAP efficiently knocks down iap gene expression and induces apoptosis phenotype and mortality in target insect species. In contrast, no significant knockdown of the iap gene expression, apoptosis phenotypes, or mortality were detected in cell lines developed from nontarget insects or nontarget insects treated with dsIAPs. Interestingly, even among closely related insects such as stink bugs, Nezara viridula, Halyomorpha halys, and Murgantia histrionica, with substantial sequence similarity among iap genes from these insects, no significant nontarget effects of dsIAP were observed under the conditions tested. These data demonstrate no significant nontarget effects for dsIAPs and suggest that the threat of nontarget effects of RNAi technology may not be substantial. 相似文献