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Heroin activates ATF3 and CytC via c-Jun N-terminal kinase pathways to mediate neuronal apoptosis.

Pu H, Wang X, Su L, Ma C, Zhang Y, Zhang L, Chen X, Li X, Wang H, Liu X, Zhang J - Med Sci Monit Basic Res (2015)

Bottom Line: RESULTS We found that heroin induces the apoptosis of primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal kinase (JNK) pathway was activated under heroin treatment and stimulated obvious increases in the levels of C-jun, Cytc, and ATF3mRNA.The results suggested that SP600125 of JNK/C-jun can inhibit heroin-induced apoptosis of neurons.CONCLUSIONS The present study analyzes our understanding of the critical role of the JNK pathway in the process of neuronal apoptosis induced by heroin, and suggests a new and effective strategy to treat SLE.

View Article: PubMed Central - PubMed

Affiliation: Department of Science and Research Education Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Sinciang, China (mainland).

ABSTRACT
BACKGROUND Drug abuse and addiction has become a major public health problem that impacts all societies. The use of heroin may cause spongiform leukoencephalopathy (SLE). MATERIAL AND METHODS Cerebellar granule cells were derived from 7-day-old Sprague-Dawley rat pups. Neurons were dissociated from freshly dissected cerebella by mechanical disruption in the presence of 0.125% trypsin and DNaseI and then seeded at a density of 4×10^6 cells/ml in Dulbecco's modified Eagle's medium/nutrient mixture F-12 ham's containing 10% fetal bovine serum and Arc-C(sigma) at concentrations to inhibit glial cell growth inoculated into 6-well plates and a small dish. RESULTS We found that heroin induces the apoptosis of primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal kinase (JNK) pathway was activated under heroin treatment and stimulated obvious increases in the levels of C-jun, Cytc, and ATF3mRNA. CYTC and ATF3 were identified as candidate targets of the JNK/c-Jun pathway in this process because the specificity inhibitors SP600125 of JNK/C-jun pathways reduced the levels of C-jun, Cytc, and ATF3mRNA. The results suggested that SP600125 of JNK/C-jun can inhibit heroin-induced apoptosis of neurons. CONCLUSIONS The present study analyzes our understanding of the critical role of the JNK pathway in the process of neuronal apoptosis induced by heroin, and suggests a new and effective strategy to treat SLE.

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Related in: MedlinePlus

Cerebellar granule cells apoptosis when maintained in 120 ug/ml heroin (H) and SP600125+120ug/ml heroin (H+S). DIV7 CGNs were then switched to medium containing 120 ug/ml heroin (B), SP600125 +120 ug/ml heroin (C). Flow cytometry show neurons apoptosis maintained in 120ug/ml heroin and SP600125 +120 ug/ml heroin for 24 h. Control cells (A) were maintained for 24 h in normal medium. The percentages of neurons apoptosis under the treatments indicated were quantified (D). Scale bar=10 um. Data represent the means ±SEM of three independent experiments.*p <0.05.
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f4-medscimonitbasicres-21-53: Cerebellar granule cells apoptosis when maintained in 120 ug/ml heroin (H) and SP600125+120ug/ml heroin (H+S). DIV7 CGNs were then switched to medium containing 120 ug/ml heroin (B), SP600125 +120 ug/ml heroin (C). Flow cytometry show neurons apoptosis maintained in 120ug/ml heroin and SP600125 +120 ug/ml heroin for 24 h. Control cells (A) were maintained for 24 h in normal medium. The percentages of neurons apoptosis under the treatments indicated were quantified (D). Scale bar=10 um. Data represent the means ±SEM of three independent experiments.*p <0.05.

Mentions: The present study showed that the JNK pathway is involved in the apoptosis process. It also indicated that the JNK/c-Jun pathway cascade was activated and amplified, leading to heroin-induced neuron apoptosis [14,27]. The rates of cell apoptosis were described by flow cytometry. We used 3 groups in our study: NM (control group), H (120 ug/ml heroin group), and H + S (120 ug/ml heroin + SP600125 inhibitor group). The results are shown in Figure 4, and indicate that the apoptosis rates in Group H were significantly higher than in group H+S (* p<0.05). The result suggests that the JNK pathway is involved in heroin-induced apoptosis.


Heroin activates ATF3 and CytC via c-Jun N-terminal kinase pathways to mediate neuronal apoptosis.

Pu H, Wang X, Su L, Ma C, Zhang Y, Zhang L, Chen X, Li X, Wang H, Liu X, Zhang J - Med Sci Monit Basic Res (2015)

Cerebellar granule cells apoptosis when maintained in 120 ug/ml heroin (H) and SP600125+120ug/ml heroin (H+S). DIV7 CGNs were then switched to medium containing 120 ug/ml heroin (B), SP600125 +120 ug/ml heroin (C). Flow cytometry show neurons apoptosis maintained in 120ug/ml heroin and SP600125 +120 ug/ml heroin for 24 h. Control cells (A) were maintained for 24 h in normal medium. The percentages of neurons apoptosis under the treatments indicated were quantified (D). Scale bar=10 um. Data represent the means ±SEM of three independent experiments.*p <0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4400970&req=5

f4-medscimonitbasicres-21-53: Cerebellar granule cells apoptosis when maintained in 120 ug/ml heroin (H) and SP600125+120ug/ml heroin (H+S). DIV7 CGNs were then switched to medium containing 120 ug/ml heroin (B), SP600125 +120 ug/ml heroin (C). Flow cytometry show neurons apoptosis maintained in 120ug/ml heroin and SP600125 +120 ug/ml heroin for 24 h. Control cells (A) were maintained for 24 h in normal medium. The percentages of neurons apoptosis under the treatments indicated were quantified (D). Scale bar=10 um. Data represent the means ±SEM of three independent experiments.*p <0.05.
Mentions: The present study showed that the JNK pathway is involved in the apoptosis process. It also indicated that the JNK/c-Jun pathway cascade was activated and amplified, leading to heroin-induced neuron apoptosis [14,27]. The rates of cell apoptosis were described by flow cytometry. We used 3 groups in our study: NM (control group), H (120 ug/ml heroin group), and H + S (120 ug/ml heroin + SP600125 inhibitor group). The results are shown in Figure 4, and indicate that the apoptosis rates in Group H were significantly higher than in group H+S (* p<0.05). The result suggests that the JNK pathway is involved in heroin-induced apoptosis.

Bottom Line: RESULTS We found that heroin induces the apoptosis of primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal kinase (JNK) pathway was activated under heroin treatment and stimulated obvious increases in the levels of C-jun, Cytc, and ATF3mRNA.The results suggested that SP600125 of JNK/C-jun can inhibit heroin-induced apoptosis of neurons.CONCLUSIONS The present study analyzes our understanding of the critical role of the JNK pathway in the process of neuronal apoptosis induced by heroin, and suggests a new and effective strategy to treat SLE.

View Article: PubMed Central - PubMed

Affiliation: Department of Science and Research Education Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Sinciang, China (mainland).

ABSTRACT
BACKGROUND Drug abuse and addiction has become a major public health problem that impacts all societies. The use of heroin may cause spongiform leukoencephalopathy (SLE). MATERIAL AND METHODS Cerebellar granule cells were derived from 7-day-old Sprague-Dawley rat pups. Neurons were dissociated from freshly dissected cerebella by mechanical disruption in the presence of 0.125% trypsin and DNaseI and then seeded at a density of 4×10^6 cells/ml in Dulbecco's modified Eagle's medium/nutrient mixture F-12 ham's containing 10% fetal bovine serum and Arc-C(sigma) at concentrations to inhibit glial cell growth inoculated into 6-well plates and a small dish. RESULTS We found that heroin induces the apoptosis of primary cultured cerebellar granule cells (CGCS) and that the c-Jun N-terminal kinase (JNK) pathway was activated under heroin treatment and stimulated obvious increases in the levels of C-jun, Cytc, and ATF3mRNA. CYTC and ATF3 were identified as candidate targets of the JNK/c-Jun pathway in this process because the specificity inhibitors SP600125 of JNK/C-jun pathways reduced the levels of C-jun, Cytc, and ATF3mRNA. The results suggested that SP600125 of JNK/C-jun can inhibit heroin-induced apoptosis of neurons. CONCLUSIONS The present study analyzes our understanding of the critical role of the JNK pathway in the process of neuronal apoptosis induced by heroin, and suggests a new and effective strategy to treat SLE.

Show MeSH
Related in: MedlinePlus