Glutamine promotes Hsp70 and inhibits α-Synuclein accumulation in pheochromocytoma PC12 cells

Abstract

Abstract. Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln-induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription-quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)-1 was required for this phenomenon with an RNA interference strategy. The regulatory role of Gln on α-Syn degeneration was also determined in the α-Syn-overexpressed PC12 [PC12 (α-Syn+)] cells, which were treated with or without the proteasomal inhibitor lactacystin (Lac). The results demonstrated that treatment with ≥10 mM Gln significantly increased Hsp70 mRNA and protein levels (P<0.05) and that this promotion was HSF-1-dependent, as HSF-1 knockout with HSF-1-specific small interfering RNA abrogated Hsp70 promotion in PC12 (α-Syn+) cells. Furthermore, Gln treatment markedly upregulated α-Syn degeneration in PC12 (α-Syn+) cells, which was significantly reduced (P<0.05) in the presence of Lac. Therefore, the present study suggests that Gln is able to induce the promotion of Hsp70 expression in PC12 cells in an HSF-1-dependent manner and that Gln-mediated Hsp70 promotion may increase α-Syn degradation even in the presence of proteasomal inhibitor. Thus, glutamine may be a potential therapeutic agent to prevent α-Syn aggregation in PD.

RETRACTED ARTICLE: 27-Hydroxycholesterol increases α-synuclein protein levels through proteasomal inhibition in human dopaminergic neurons

“…In addition to their role in cellular stress, they are involved in the disassembly of protein aggregates and targeting of proteins for degradation. Increasing HSP70 has been shown to inhibit α-syn accumulation in PC12 cells [ 35 ]. In this study we aimed to investigate the effects of 27-OHC on both UPS and HSP70 protein levels.…”

Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model

“…Glutamine, as the most abundant free amino acid, has been proved to be closely related to the occurrence and development of neurodegenerative diseases [19]. Wang et al reported that glutamine could inhibit alpha-Synuclein accumulation to protect cells against degeneration in the PD cell model [20]. In the present study, our results showed that the MPP + displayed obvious cytotoxicity on PC12 cells, while glutamine could increase the viability of PC12 cells through suppressing neurotoxicity induced by MPP + .…”

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

“…Ellagic acid [214] Entacapone (Comtan, ASI-6) [12,215,216] Enzastaurin [164] Epicatechin [128,160,193,194] Epigallocatechin-3-gallate [117,217,218] Etidronate (HEDPA) [219] Exifone [12] F13714 [220] F15599 [220,221] Farrerol [222] Fisetin (3,3 ,4 ,7-Tetrahydroxy flavone) [223][224][225] Fraxetin [117] Galangin [226] Gallic acid and derivatives [214,227,228] Gallocatechin [128] Garcinol [229] Genistein [117,128,230,231] Glutamine [232] Glutathione derivatives [63] Glutathione -hydroxyquinoline compound [233] Glutathione-l-DOPA compound [234] Gly-N-C-DOPA [209] GSK2795039 [108] Guanabenz [235] Hesperidin [128,236] Hinokitiol […”