Carnosic Acid Protects Mitochondria of Human Neuroblastoma SH-SY5Y Cells Exposed to Paraquat Through Activation of the Nrf2/HO-1Axis.
Carnosic acid (CA; C20H28O4), which is also called salvin, is a major phenolic diterpene found in Rosmarinus officinalis L. and exhibits antioxidant, anti-inflammatory, and antiproliferative properties. CA activates the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, leading to the upregulation of antioxidant and phase II detoxification enzymes, such as heme oxygenase-1 (HO-1), glutathione reductase (GR), γ-glutamate-cysteine ligase (γ-GCL), and glutathione S-transferase (GST), among others. We have previously demonstrated that CA upregulates the total and mitochondrial synthesis of glutathione (GSH), causing mitochondrial protection against paraquat (PQ) and methylglyoxal (MG). Nonetheless, the complete mechanism by which CA prevented mitochondrial dysfunction was not clear yet. Here, we examine whether HO-1 would be involved in the CA-induced mechanism of mitochondrial protection in SH-SY5Y-treated cells. SH-SY5Y cells were pretreated with CA (1 μM) for 12 h prior to a challenge with PQ at 100 μM for additional 24 h. Zinc protoporphyrin IX (ZnPP IX; a specific inhibitor of HO-1; 10 μM) was utilized prior to exposure to CA in order to investigate whether HO-1 was involved in the cytoprotective effects elicited by CA. We found that the CA-induced Nrf2-dependent HO-1 upregulation ameliorated, at least in part, the mitochondrial function in PQ-treated cells. Therefore, CA protected mitochondria of SH-SY5Y cells and exerted anti-apoptotic effects by activating the Nrf2/HO-1 axis.
Department of Chemistry/ICET, Federal University of Mato Grosso (UFMT), Av. Fernando Corrêa da Costa, 2367, CEP 78060-900, Cuiaba, MT, Brazil. mrobioq@gmail.com.
Marcos Roberto
MR
de Oliveira
Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.|Centro de Pesquisa da Pós-Graduação, Centro Universitário Metodista IPA, Porto Alegre, RS, 90420-060, Brazil.
Alessandra
A
Peres
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Gustavo Costa
GC
Ferreira
Laboratório de Erros Inatos do Metabolismo, Unidade Acadêmica de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense (UNESC), Criciúma, SC, Brazil.
Patrícia Fernanda
PF
Schuck
Laboratório de Psiquiatria Molecular, Hospital de Clínicas de Porto Alegre (HCPA), Instituto Nacional de Ciência e Tecnologia - Medicina Translacional (INCT-TM), Porto Alegre, RS, Brazil.|Programa de Pós-Graduação em Medicina: Psiquiatria, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Clarissa S
CS
Gama
Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil.
Simone Morelo Dal
SMD
Bosco
D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D045784:Abietanes; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C018381:salvin
Anti-apoptotic; Antioxidant; Carnosic acid; HO-1; Mitochondria
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