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Morphological changes of apoptotic cells. (a) In the apoptotic cell, cytoplasm was intensely eosinophilic, and nucleus is shrunken and dense ring-shaped (↑). (H·E × 1000); and (b) In the apoptotic cell, nucleus is crescentic (↑). (H·E × 1000); (c) and (d) In the apoptotic cells, nuclei are cracked into two or multiple apoptotic bodies (↑). (H·E × 1000).
Source publication
Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-t...
Citations
... Beside its role in CREB activation, Nrf2 stimulation and M1/M2 polarization, the PI3K/AKT pathway is also the upstream activator of Bcl-2, the anti-apoptotic protein (Guo et al., 2015). Stimulation of PI3K/AKT pathway leads to significant increase in Bcl-2 level, an important apoptotic suppressor protein (Guo et al., 2015). ...
... Beside its role in CREB activation, Nrf2 stimulation and M1/M2 polarization, the PI3K/AKT pathway is also the upstream activator of Bcl-2, the anti-apoptotic protein (Guo et al., 2015). Stimulation of PI3K/AKT pathway leads to significant increase in Bcl-2 level, an important apoptotic suppressor protein (Guo et al., 2015). The involvement of PI3K/AKT/Bcl-2 signaling in the α7-nAChR-mediated anti-apoptotic and neuroprotective effects has been reported. ...
Fibromyalgia (FM) is a pain disorder marked by generalized musculoskeletal pain accompanied by depression, fatigue, and sleep disturbances. Galantamine (Gal) is a positive allosteric modulator of neuronal nicotinic acetylcholine receptors (nAChRs) and a reversible inhibitor of cholinesterase. The current study aimed to explore the therapeutic potential of Gal against reserpine (Res)-induced FM-like condition along with investigating the α7-nAChR's role in Gal-mediated effects. Rats were injected with Res (1 mg/kg/day; sc) for 3 successive days then Gal (5 mg/kg/day; ip) was given alone and with the α7-nAChR blocker methyllycaconitine (3 mg/kg/day; ip), for the subsequent 5 days. Galantamine alleviated Res-induced histopathological changes and monoamines depletion in rats' spinal cord. It also exerted analgesic effect along with ameliorating Res-induced depression and motor-incoordination as confirmed by behavioral tests. Moreover, Gal produced anti-inflammatory effect through modulating AKT1/AKT2 and shifting M1/M2 macrophage polarization. The neuroprotective effects of Gal were mediated through activating cAMP/PKA and PI3K/AKT pathways in α7-nAChR-dependent manner. Thus, Gal can ameliorate Res-induced FM-like symptoms and mitigate the associated monoamines depletion, neuroinflammation, oxidative stress, apoptosis, and neurodegeneration through α7-nAChR stimulation, with the involvement of cAMP/PKA, PI3K/AKT, and M1/M2 macrophage polarization.
... The concentration in healthy persons as control were still less than that of CKD patients in urine and blood of both male and females with the concentration of (0.066mg/l, 0.023mg/l 0.012mg/l and 0.110mg/l) respectively. It was reported that excess Ni has been shown to trigger an inflammatory response by activating nuclear factor-kB and tubular apoptosis through the phosphoinositide 3-kinase (PI3K)-RAC serine/threonine-protein kinase (AKT) pathway (Xu et al., 2018: Guo et al., 2015. ...
... The PI3K/Akt pathway is an important pathway that regulates protein synthesis, cell cycle progression, proliferation, apoptosis, and cytokine stimulation [52,53]. Akt activated by PI3K is the main mediator of signal transduction in this pathway, and the amount of phosphorylated AKT influences the proliferation and survival of cells [54,55]. In order to study the ability of coix seed oil to regulate the PI3K/Akt signaling pathway in HT-29 colon cancer cells, the mRNA and protein levels of PI3K and Akt were detected by RT-PCR and Western blot analysis. ...
This study aims to observe the effects of coix seed oil (CSO) on HT-29 cells and investigate its possible regulation mechanism of the PI3K/Akt signaling pathway. Fatty acid analysis showed that coix seed oil mainly contains oleic acid (50.54%), linoleic acid (33.76%), palmitic acid (11.74%), and stearic acid (2.45%). Fourier transform infrared results found that the fatty acid functional groups present in the oil matched well with the vegetable oil band. The results from CCK-8 assays showed that CSO dose-dependently and time-dependently inhibited the viability of HT-29 cells in vitro. CSO inhibited cell viability, with IC50 values of 5.30 mg/mL for HT-29 obtained after 24 h treatment. Morphological changes were observed by apoptotic body/cell nucleus DNA (Hoechst 33258) staining using inverted and fluorescence microscopy. Moreover, flow cytometry analysis was used to evaluate the cell cycle and cell apoptosis. It showed that CSO induced cell apoptosis and cycle arrest in the G2 phase. Quantitative real-time PCR and Western blotting revealed that CSO induced cell apoptosis by downregulating the PI3K/AKT signaling pathway. Additionally, CSO can cause apoptosis in cancer cells by activating caspase-3, up-regulating Bax, and down-regulating Bcl-2. In conclusion, the results revealed that CSO induced G2 arrest and apoptosis of HT-29 cells by regulating the PI3K/AKT signaling pathway.
... With the increasing incidence of Ni contamination in recent years, human Ni toxicity attracted more attention (Caggiano et al. 2019;Das et al. 2018). Our previous investigations have shown that Ni toxicological effects include immunotoxicity Huang et al. 2013b;Tang et al. 2015;Tang et al. 2014;Wu et al. 2014a, b;Wu et al. 2015a;Wu et al. 2013;Wu et al. 2014c;Yin et al. 2016a;Yin et al. 2016b), hepatotoxicity , nephrotoxicity (Guo et al. 2015a;Guo et al. 2016c;Guo et al. 2015bGuo et al. , 2016dGuo et al. 2015c), pulmonary toxicity (Deng et al. 2016), genotoxicity, neurotoxicity, and reproductive toxicology (Bisceglie et al. 2019;Ijomone et al. 2018;Kong et al. 2017;Owumi et al. 2019). Ni and its compounds have been confirmed as human carcinogens by the International Agency for Research on Cancer (IARC) and the U.S. Department of Health and Human Services (Pesch et al. 2019;Puangprasert and Prueksasit 2019). ...
Nickel (Ni) is a widely distributed metal in the environment and an important pollutant due to its widespread industrial applications. Ni has various toxicity in humans and experimental animals, including carcinogenicity. However, the carcinogenic effects of Ni remain troublesome. Cell cycle dysregulation may be an important carcinogenic mechanism and is also a potential molecular mechanism for Ni complexes anti-cancerous effects. Therefore, we conducted a literature review to summarize the effects of Ni on cell cycle. Up to now, there were three different reports on Ni-induced cell cycle arrest: (i) Ni can induce cell cycle arrest in G0/G1 phase, phosphorylation and degradation of IkappaB kinase-alpha (IKKα)–dependent cyclin D1 and phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway–mediated down-regulation of expressions of cyclin-dependent kinases 4 (CDK4) play important role in it; (ii) Ni can induce cell cycle arrest in S phase, but the molecular mechanism is not known; (iii) G2/M phase is the target of Ni toxicity, and Ni compounds cause G2/M cell cycle phase arrest by reducing cyclinB1/Cdc2 interaction through the activation of the ataxia telangiectasia mutated (ATM)-p53-p21 and ATM-checkpoint kinase inhibitor 1 (Chk1)/Chk2-cell division cycle 25 (Cdc25) pathways. Revealing the mechanisms of cell cycle dysregulation associated with Ni exposure may help in the prevention and treatment of Ni-related carcinogenicity and toxicology.
... The PI3K signaling regulates not only growth and proliferation but also angiogenesis, cell survival and apoptosis. Transcription factors NFKB1, NFKB2, TGFB2 66 , MYC 67 and BCL2L2 68 have also been associated with apoptosis and cell survival in the PI3K signaling cascade. Post mortem proteolysis is mainly governed by the physiological processes of cell survival and apoptosis that contribute to tenderization of muscle protein 21,69 . ...
The study presents the miRNA profiles of two Indian sheep populations with divergent carcass and muscle traits. The RNA sequencing of longissimus thoracis muscles from the two populations revealed a total of 400 known miRNAs. Myomirs or miRNAs specific to skeletal muscles identified in our data included oar-miR-1, oar-miR-133b, oar-miR-206 and oar-miR-486. Comparison of the two populations led to identification of 100 differentially expressed miRNAs (p < 0.05). A total of 45 miRNAs exhibited a log2 fold change of ≥ ( ±) 3.0. Gene Ontology analysis revealed cell proliferation, epithelial to mesenchymal transition, apoptosis, immune response and cell differentiation as the most significant functions of the differentially expressed miRNAs. The differential expression of some miRNAs was validated by qRT-PCR analysis. Enriched pathways included metabolism of proteins and lipids, PI3KAkt, EGFR and cellular response to stress. The microRNA-gene interaction network revealed miR-21, miR-155, miR-143, miR-221 and miR-23a as the nodal miRNAs, with multiple targets. MicroRNA-21 formed the focal point of the network with 42 interactions. The hub miRNAs identified in our study
form putative regulatory candidates for future research on meat quality traits in Indian sheep. Our results provide insight into the biological pathways and regulatory molecules implicated in muscling
traits of sheep.
... On binding to its receptor, G-CSF activates intracellular pathways, the major pathway being the PI3K/AKT pathway [20]. Activated AKT promotes neuroprotection in the ischemic brain [53,54] pAkt inhibits several apoptotic substrates, such as caspase 9, and Bad [55], as well as increasing the expression level of Bcl-2, Bcl-xL (anti-apoptotic proteins) and decreases Bax expression level (pro-apoptotic protein) [56]. Here we demonstrated that hG-CSF gene markedly upregulated pAKT 4-and 7-days post-ischemia, indicating that the expressed hG-CSF gene elicits neuroprotection, at least in part, via the PI3K/AKT pathway. ...
Background
Global ischemia is the resulting effect of a cardiopulmonary arrest (CPA). Presently there is no effective treatment to address neurological deficits in patients who survived a CPA. Granulocyte-colony stimulating factor is a growth factor (G-CSF) with a plethora of beneficial effects, including neuroprotection. Clinical application of human G-CSF (hG-CSF) is limited due to its plasma half-life of 4 h. Therefore, novel approaches need to be investigated that would (1) enable prolonged manifestation of hG-CSF and (2) demonstrate G-CSF efficacy from studying the underlying protective mechanisms of hG-CSF. In our previous work, we used the self-complementary adeno-associated virus (stereotype2: scAAV2) as a vector to transfect the hG-CSF gene into the global ischemic brain of a mouse. As an extension of that work, we now seek to elucidate the protective mechanisms of hG-CSF gene therapy against endoplasmic reticulum induced stress, mitochondrial dynamics and autophagy in global ischemia.
Method
A single drop of either AAV-CMV-hG-CSF or AAV-CMV-GFP was dropped into the conjunctival sac of the Swiss Webster mouse’s left eye, 30–60 min after bilateral common artery occlusion (BCAO). The efficacy of the expressed hG-CSF gene product was analyzed by monitoring the expression levels of endoplasmic reticulum stress (ER), mitochondrial dynamics and autophagic proteins over 4- and 7-days post-BCAO in vulnerable brain regions including the striatum, overlying cortex (frontal brain regions) and the hippocampus (middle brain regions). Statistical analysis was performed using mostly One-Way Analysis of variance (ANOVA), except for behavioral analysis, which used Repeated Measures Two-Way ANOVA, post hoc analysis was performed using the Tukey test.
Results
Several biomarkers that facilitated cellular death, including CHOP and GRP78 (ER stress) DRP1 (mitochondrial dynamics) and Beclin 1, p62 and LC3-ll (autophagy) were significantly downregulated by hG-CSF gene transfer. hG-CSF gene therapy also significantly upregulated antiapoptotic Bcl2 while downregulating pro-apoptotic Bax. The beneficial effects of hG-CSF gene therapy resulted in an overall improvement in functional behavior.
Conclusion
Taken together, this study has substantiated the approach of sustaining the protein expression of hG-CSF by eye drop administration of the hG-CSF gene. In addition, the study has validated the efficacy of using hG-CSF gene therapy against endoplasmic reticulum induced stress, mitochondrial dynamics and autophagy in global ischemia.
... The PI3K signaling regulates not only growth and proliferation but also angiogenesis, cell survival and apoptosis. Transcription factors NFKB1, NFKB2, TGFB2 66 , MYC 67 and BCL2L2 68 have also been associated with apoptosis and cell survival in the PI3K signaling cascade. Post mortem proteolysis is mainly governed by the physiological processes of cell survival and apoptosis that contribute to tenderization of muscle protein 21,69 . ...
The study presents the miRNA profiles of two Indian sheep populations with divergent carcass and muscle traits. The RNA sequencing of longissimus thoracis muscles from the two populations revealed a total of 400 known miRNAs. Myomirs or miRNAs specific to skeletal muscles identified in our data included oar-miR-1, oar-miR-133b, oar-miR-206 and oar-miR-486. Comparison of the two populations led to identification of 100 differentially expressed miRNAs (p < 0.05). A total of 45 miRNAs exhibited a log 2 fold change of ≥ ( ±) 3.0. Gene Ontology analysis revealed cell proliferation, epithelial to mesenchymal transition, apoptosis, immune response and cell differentiation as the most significant functions of the differentially expressed miRNAs. The differential expression of some miRNAs was validated by qRT-PCR analysis. Enriched pathways included metabolism of proteins and lipids, PI3K-Akt, EGFR and cellular response to stress. The microRNA-gene interaction network revealed miR-21, miR-155, miR-143, miR-221 and miR-23a as the nodal miRNAs, with multiple targets. MicroRNA-21 formed the focal point of the network with 42 interactions. The hub miRNAs identified in our study form putative regulatory candidates for future research on meat quality traits in Indian sheep. Our results provide insight into the biological pathways and regulatory molecules implicated in muscling traits of sheep.
... The method used was that described by Hongrui Guo et al. [27]. Slices were dewaxed and washed in distilled water and then incubated with 3% H 2 O 2 in methanol for 15 min. ...
To study the toxicity induced by Nickel sulfate (NiSO4) on thyroid tissue, and investigate the role of apoptosis as the possible mechanism, thirty-two male Wistar rats were randomly divided into control group (normal saline, ip), low dose group (2.5 mg/kg day NiSO4, ip), middle dose group (5 mg/kg day NiSO4, ip), high dose group (10 mg/kg day NiSO4, ip). After 40 consecutive days of treatment, there were obvious pathological changes in the thyroids of high dose group. Free T4 (FT4) and thyroid-stimulating hormone (TSH) were significantly lower in the NiSO4-treated groups than those in the control group (F = 4.992, p = 0.016; F = 4.524, p = 0.012). The mRNA expression of Caspase-3 was significantly higher (F = 10.259, p = 0.014) in all NiSO4-treated groups, and the mRNA expression of Bcl-2 was significantly lower (F = 9.225, p = 0.018) only in the high dose group. Both control group and the NiSO4-treated groups showed no changes in the mRNA expression of Bax gene. The ratio of Bcl-2/Bax decreased with the increase in exposure dose of NiSO4 (F = 13.382, p = 0.015). The mRNA expression of Fas went up in high dose group (F = 66.632, p < 0.001). The Caspase-3, Fas, and the Bax protein expressions measured by immunohistochemistry were consistent with the mRNA expression. The expression of Bcl-2 protein was significantly lower in the test groups than in the control group (F = 3.873, p = 0.025). NiSO4 as an Endocrine Disrupting Chemical may induce the thyroid injury through apoptosis and lead to hypothyroidism. Also, apoptosis in thyroid tissues was closely related to the alternations of Caspase-3, Bcl-2, and Fas mRNA and protein expression.
... As the direct target gene of miR-21 and miR-31, the T lymphoma and metastasis gene 1 (TIAM1) have been found to regulate the migration and invasion of colon carcinoma cells (Cottonham et al., 2010). The activity of proapoptotic proteins is frequently repressed via oncogenic kinases such as PI3K/AKT and consequently, these kinases lead to the inactivation of Bak and Bax genes (Guo et al., 2015). Malignant cells have several mechanisms to escape apoptosis. ...
Colorectal cancer (CRC) is the main cause of cancer-related mortalities, worldwide and is the most prevalent cancer of the gastrointestinal tract. Different techniques exist to diagnose CRC including colonoscopy, sigmoidoscopy, and plasma miRNA test. This study evaluates the important miRNAs and main genes playing role in metastasis, angiogenesis and apoptosis that can be considered as prognostic and progression markers of CRC. We have measured the expression levels of the miRNAs, and multiple genes related to angiogenesis, metastasis and apoptosis in 45 paired samples of CRC tissue specimens and adjacent normal mucosa tissues obtained from 45 patients with CRC utilizing Real-time PCR. We have also analyzed the relationship between the expression of these genes and clinic pathological features. Results showed that the expression levels of angiogenesis genes (PGE-2, VEGF, Vimentin, CD105, CXCL-1, and IGFBP-7), metastatic genes (IGF-1R, Snail-1, and MMP-7) and apoptotic genes (Bcl-2, Bcl-xl, and NF-κβ1) were significantly higher in cancer tissues. But the expression levels of E-cadherin, AdipoR1, Claudin-7, Bax, Puma, and Noxa, were notably lower in cancer tissues. Additionally, it was revealed that miRNAs (miR-21, miR-19a, miR-18a, and miR-92a) expression levels were in higher levels in cancer tissues when compared to the normal tissues. In contrast, the expression levels of miR-31, and miR-139-5p were significantly lower in cancer tissues. It is hoped that, by measuring the metastasis, angiogenesis and apoptosis resistance associated miRNAs expression, better treatment results would be achieved in CRC treatment.
... Gastric cancer is associated with the inactivation of tumor suppressor genes (7). Recent studies have demonstrated that the Wnt signaling pathway is abnormally activated in certain types of cancer (7,8). Glycogen synthase kinase-3β (GSK3β) is an important molecule involved in the Wnt signaling pathway, which is a serine/threonine kinase involved in the regulation of microtubule dynamics, proliferation, apoptosis, angiogenesis and cell motility, as well as other functions (9). ...
... Following various types of cell stress signal, the pro-apoptotic proteins in the Bcl-2 gene family are activated and interact with anti-apoptotic proteins to inactivate the cell (8). The anti-apoptotic and pro-apoptotic members in the Bcl-2 family proteins possess conserved α-helix and homologous domains (23). ...
The aim of the present study was to investigate the anticancer effect of resibufogenin in gastric carcinoma cells through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3β (GSK3β) signaling pathway. MGC-803 cells were treated with 0, 1, 2, 4 and 8 µM resibufogenin for 12, 24 and 48 h. Cell viability and apoptosis were measured using an MTT assay and annexin V staining. Caspase-3 and caspase-8 activity were identified using caspase-3 and caspase-8 activity kits and a variety of protein expression [B cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), cyclin D1, cyclin E, PI3K, phosphorylated AKT, phosphorylated GSK3β and β-catenin] were quantified using western blot analysis. It was revealed that resibufogenin effectively inhibited cell proliferation, and induced apoptosis and caspase-3 and caspase-8 activity in MGC-803 cells. Furthermore, treatment with resibufogenin effectively increased Bax/Bcl-2 expression, and suppressed cyclin D1, cyclin E, PI3K, phosphorylated AKT, phosphorylated GSK3β and β-catenin protein expression in MGC-803 cells. These results suggest that the anticancer effect of resibufogenin induces gastric carcinoma cell death through the PI3K/AKT/GSK3β signaling pathway, offering a novel view of the mechanism by which resibufogenin functions as an agent to treat gastric carcinoma.
