Heroin Activates ATF3 and CytC via c-Jun N-Terminal Kinase Pathways to Mediate Neuronal Apoptosis

Pu, Hongwei; Wang, Xuemei; Su, Liping; Ma, Chuang; Zhang, Yan; Zhang, Liping; Chen, X; Li, Xiujuan; Wang, Hua; Liu, Xiaoshan; Zhang, Jianlong

doi:10.12659/msmbr.893827

Cited by 20 publications

(9 citation statements)

References 35 publications

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“…All of the genes upregulated in response to SEC have potential links with apoptosis. ATF3 has low expression in normal cells and upregulated with stress signals involved in apoptosis [ 39 – 41 ]. Accumulating studies indicate that ATF3 may work as a master regulator controlling the expression of PPP1R15A [ 29 , 42 ], IL8 [ 30 ] and TRIB3 [ 31 , 32 , 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

A small molecule induces integrin β4 nuclear translocation and apoptosis selectively in cancer cells with high expression of integrin β4

et al. 2016

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Increased integrin β4 (ITGB4) level is accompanied by malignant progression of multiple carcinomas. However, selective therapeutic strategies against cancer cells expressing a high level of ITGB4 have not been reported. Here, for the first time, we report that a chiral small molecule, SEC, selectively promotes apoptosis in cancer cells expressing a high level of ITGB4 by inducing ITGB4 nuclear translocation. Nuclear ITGB4 can bind to the ATF3 promoter region and activate the expression of ATF3, then upregulate the downstream pro-apoptosis genes. Furthermore, SEC promoted the binding of annexin A7 (ANXA7) to ITGB4 and increased ANXA7 GTPase activity. Activated ANXA7 promoted ITGB4 nuclear translocation by triggering ITGB4 phosphorylation at Y1494. SEC also inhibited the growth of xenograft tumors in the avian embryo model. We identified a small molecule, SEC, with selective pro-apoptosis effects on cancer cells with high expression of ITGB4, both in vitro and in vivo, by triggering the binding of ITGB4 and ANXA7, ITGB4 nuclear trafficking, and pro-apoptosis gene expression.

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Section: Discussionmentioning

confidence: 99%

A small molecule induces integrin β4 nuclear translocation and apoptosis selectively in cancer cells with high expression of integrin β4

et al. 2016

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“…In addition, although some of the infections are due to passing the pathogens among HDPs through shared needles and unprotected sexual behaviors, chronic heroin abuse and addiction may result in permanent neuronal impairment in HDPs. In animal models, increased cerebellar neuronal apoptosis was observed in heroin-addicted rats 6 , 7 , possibly by activating the c-Jun kinase signaling and related pathways 8 , 9 . Mice that exposed to heroin prenatally showed reduced exploration for objects in novel locations indicating alterations in pyramidal neurons 10 .…”

Section: Introductionmentioning

confidence: 99%

Heroin Abuse Results in Shifted RNA Expression to Neurodegenerative Diseases and Attenuation of TNFα Signaling Pathway

Zhu

Wang

et al. 2018

Sci Rep

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Repeated administration of heroin results in the induction of physical dependence, which is characterized as a behavioral state of compulsive drug seeking and a high rate of relapse even after periods of abstinence. However, few studies have been dedicated to characterization of the long-term alterations in heroin-dependent patients (HDPs). Herein, we examined the peripheral blood from 810 HDPs versus 500 healthy controls (HCs) according to the inclusion criteria. Compared with the control group, significant decreases of albumin, triglyceride, and total cholesterol levels were identified in HDPs (P < 0.001) versus HCs coupled with an insignificant decrease in BMI. Meanwhile, RNA-sequencing analyses were performed on blood of 16 long-term HDPs and 25 HCs. The results showed that the TNFα signaling pathway and hematopoiesis related genes were inhibited in HDPs. We further compared the transcriptome data to those of SCA2 and posttraumatic stress disorder patients, identified neurodegenerative diseases related genes were commonly up-regulated in coupled with biological processes “vesicle transport”, “mitochondria” and “splicing”. Genes in the categories of “protein ubiquitination” were down-regulated indicating potential biochemical alterations shared by all three comparative to their controls. In summary, this is a leading study performing a series of through investigations and using delicate approaches. Results from this study would benefit the study of drug addiction overall and link long-term heroin abuse to neurodegenerative diseases.

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“…They control the fundamental cellular processes of growth, proliferation, differentiation, and cell death when activated by environmental stresses and inflammatory stimuli [14,15]. It has been reported that the MAPKs signal pathways also play a critical role in BBR-mediated regulation of virus replication [13,16].…”

Section: Introductionmentioning

confidence: 99%

Berberine Restricts Coxsackievirus B Type 3 Replication via Inhibition of c-Jun N-Terminal Kinase (JNK) and p38 MAPK Activation In Vitro

Dai

Zhang

et al. 2017

Med Sci Monit

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BackgroundAt present, the treatment of coxsackievirus-induced myocarditis remains difficult. Berberine (BBR), an isoquinoline alkaloid isolated from traditional medicine herbs, exhibits significant anti-viral efficacy against various viruses. However, the underlying mechanism by which BBR controls CVB3 infection has not yet been reported. The purpose of this study was to investigate the anti-viral efficacy of BBR against CVB3 infection and its mechanism.Material/MethodsIn our experiments, the protein levels of VP1 and MAPKs signal pathway were measured by Western blot. The mRNA level of VP1 was measured by RT-PCR. The virus titers were determined by TCID50 assay.ResultsWe found that BBR treatment significantly decreased CVB3 replication in HeLa cells. In addition, the BBR treatment reduced the phosphorylation levels of JNK and p38 MAPK upon CVB3 infection in both HeLa cells and primary rat myocardial cells.ConclusionsTaken together, these results suggest that BBR inhibits CVB3 replication through the suppression of JNK and p38 MAPK activation, shedding new light on the investigation of therapeutic strategies against CVB3-induced viral myocarditis.

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Heroin Activates ATF3 and CytC via c-Jun N-Terminal Kinase Pathways to Mediate Neuronal Apoptosis

Cited by 20 publications

References 35 publications

A small molecule induces integrin β4 nuclear translocation and apoptosis selectively in cancer cells with high expression of integrin β4

A small molecule induces integrin β4 nuclear translocation and apoptosis selectively in cancer cells with high expression of integrin β4

Heroin Abuse Results in Shifted RNA Expression to Neurodegenerative Diseases and Attenuation of TNFα Signaling Pathway

Berberine Restricts Coxsackievirus B Type 3 Replication via Inhibition of c-Jun N-Terminal Kinase (JNK) and p38 MAPK Activation In Vitro

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