Methyl Jasmonate Protects Microglial Cells Against β-Amyloid-Induced Oxidative Stress and Inflammation via Nrf2-Dependent HO-1 Pathway
Authors Li H, Lv L, Wu C, Qi J, Shi B
Received 4 December 2019
Accepted for publication 31 March 2020
Published 4 June 2020 Volume 2020:16 Pages 1399—1410
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 5
Editor who approved publication: Dr Yuping Ning
Hua Li,1,* Limei Lv,2,* Chunyan Wu,3 Jisheng Qi,4 Baolin Shi5
1Department of Neurology, Anqiu People’s Hospital, Anqiu 262100, Shandong, People’s Republic of China; 2Department of Neurology, Traditional Chinese Medical Hospital of Anqiu, Anqiu 262100, People’s Republic of China; 3Department of Neurology, Affiliated Hospital of Weifang Medical College, Weifang 261031, Shandong, People’s Republic of China; 4Department of Rehabilitation Medicine, Shandong Rongjun General Hospital, Jinan 250000, Shandong, People’s Republic of China; 5Department of Neurology, Weifang People’s Hospital, Weifang 261031, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Baolin Shi
Department of Neurology, Weifang People’s Hospital, No. 151 Guangwen Street, Kuiwen District, Weifang 261031, Shandong, People’s Republic of China
Background: β-Amyloid (Aβ) induces oxidative stress and inflammation of microglial cells, thus leading to Alzheimer’s disease. Methyl jasmonate (MeJA) is reported to have anti-inflammatory and anti-oxidant effects. However, the potential roles of MeJA in Aβ-induced cell activities and the underlying mechanism are unclear.
Methods: Microglial cell line BV-2 was stimulated by 20 μM Aβ and/or 20 μM MeJA and then divided into four groups (control, Aβ, MeJA, and Aβ+MeJA). Cell viability was detected by MTT assay. MDA, SOD activity, and ROS were detected by fluorescence spectrophotometry and immunofluorescence assay. Nrf2 and HO-1 were detected by qRT-PCR and Western blot. Furthermore, inflammatory cytokines (p-NFκB, TLR4, TNF-α, IL-1β, and IL-6) and apoptosis factors (Bcl-2, Bax, and cl-casp-3) were detected by Western blot. TUNEL assay was applied to investigate apoptosis rate. Moreover, the mechanism of how MeJA played anti-oxidative stress and anti-inflammatory roles was investigated by silencing of Nrf2 via siRNA.
Results: The result of MTT assay showed that MeJA improved the decreased viability of BV-2 cells induced by Aβ. The detection of MDA, SOD activity, and ROS showed the oxidative stress levels were decreased in Aβ+MeJA group compared with Aβ group. Nrf2, HO-1, and SOD were significantly up-regulated in Aβ+MeJA group compared with Aβ group (p< 0.01). In contrast, inflammatory cytokines were significantly down-regulated in Aβ+MeJA group compared with Aβ group (p< 0.05). Similarly, the expressions of apoptosis cytokines and TUNEL assay suggested a decreased apoptosis rate in Aβ+MeJA group compared to Aβ group (p< 0.01). Finally, results of Nrf2 knockdown experiment showed down-regulations of anti-oxidative stress factors (Nrf2, HO-1 and SOD), up-regulations of inflammatory cytokines, and increased ratio of Bax to Bcl in Aβ+MeJA+si-Nrf2 group compared with Aβ+MeJA group (p< 0.01).
Conclusion: MeJA could relieve Aβ-induced oxidative stress and inflammatory response in microglial cells by activating Nrf2/HO-1 pathway.
Keywords: methyl jasmonate, Nrf2-dependent HO-1 pathway, β-amyloid, oxidative stress, inflammatory cytokines
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