Inhibition of JNK by pi class of glutathione S-transferase through PKA/CREB pathway is associated with carnosic acid protection against 6-hydroxydopamine-induced apoptosis. (May 2017)

• Record Type: Journal Article
• Authors: Lin, Chia-Yuan; Fu, Ru-Huei; Chou, Ruey-Hwang; Chen, Jing-Hsien; Wu, Chi-Rei; Chang, Shu-Wei; Tsai, Chia-Wen
• Is Part Of: Food and chemical toxicology. Volume 103(2017)
• Page Start: 194
• Page End: 202
• Publication Date: 2017-05
• Subjects: Carnosic acid -- Protein kinase A pathway -- Pi class of glutathione -- S-transferase -- c-Jun N-Terminal kinase -- SH-SY5Y cells; CA carnosic acid -- CRE cAMP response element -- CREB cAMP response element binding protein -- DMSO dimethyl sulfoxide -- EMSA electromobility gel shift assay -- GST glutathione S-transferase -- GSTA alpha class of glutathione S-transferase -- GSTM mu class of glutathione S-transferase -- GSTP pi class of glutathione S-transferase -- 6-OHDA 6-hydroxydopamine -- JNK c-Jun N-terminal kinase -- MAPKs mitogen-activated protein kinases -- MPTP 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine -- NF-κB nuclear factor κB -- PARP poly-ADP ribose polymerase -- PD Parkinson's disease -- PI3K/Akt phosphatidylinositide 3-kinase/protein kinase -- PKA protein kinase A -- siRNA small interfering RNA; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2017.03.020
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Pi class of glutathione S -transferase (GST) is known to suppress c-Jun N-terminal kinase (JNK)-related apoptosis through protein-protein interactions. Moreover, signaling by PKA/cAMP response element binding protein (CREB) is necessary for GSTP up-regulation. This study explored whether carnosic acid (CA) from rosemary prevents 6-hydroxydopamine (6-OHDA)-induced neurotoxicity by inhibition of JNK through GSTP via PKA/CREB signaling. Results indicated that the GSTP protein was increased in SH-SY5Y cells treated with CA for 18 and 24 h. However, CA had no significant effect on alpha or mu class of GST. Treatment of CA increased the induction of p-PKAα, nuclear p-CREB, and CRE-DNA binding activity. These effects of CA were attenuated in cells pretreated with the PKA inhibitor H89. CA pretreatment suppressed 6-OHDA-induced apoptosis by inhibition of JNK phosphorylation, poly(ADP)-ribose polymerase cleavage, and nuclear condensation. Pretreatment with H89 and GSTP siRNA attenuated the ability of CA to reverse 6-OHDA-induced apoptosis. By use of immunoprecipitation with JNK antibody to examine the interaction of GSTP-JNK with CA, we showed that CA pretreatment increased the immunoprecipitation of GSTP after 6-OHDA treatment, which suggests that CA promoted the interaction between GSTP and JNK. Conclusion: CA prevents 6-OHDA-induced apoptosis via inhibition of JNK by GSTP through the PKA/CREB pathway. Graphical abstract: Highlights: The up-regulation of GSTP caused by CA is dependent on the PKA/CREB pathway in SH-SY5Y cells. CA protects against 6-OHDA-induced apoptosis of SH-SY5Y cells by activating PKA/CREB/GSTP pathway. CA inhibited JNK-related apoptosis through the enhancement of GSTP-JNK interaction in 6-OHDA-treated cells.