Protective effects of DJ-1 medicated Akt phosphorylation on mitochondrial function are promoted by Da-Bu-Yin-Wan in 1-methyl-4-phenylpyridinium-treated human neuroblastoma SH-SY5Y cells

Zhang, Yi; Gong, Xiao-Gang; Wang, Zhenzhen; Sun, Haixiang; Guo, Zhenyu; Gai, Cong; Hu, Jing‐Hong; Ma, Ling; Li, Ping; Chen, Nai‐Hong

doi:10.1016/j.jep.2016.04.029

Cited by 14 publications

(5 citation statements)

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“…The PI3K/AKT signaling pathway is a classic signaling cascade that regulates cell growth and proliferation by affecting a multitude of complementary downstream pathways. The previous studies revealed that DJ-1 could increase the AKT phosphorylation and activated the PI3K/AKT signaling pathway in human (Yang et al, 2005; Zhang et al, 2016). However, it has rarely been reported in fungi.…”

Section: Resultsmentioning

confidence: 98%

ASF1 activation PI3K/AKT pathway regulates sexual and asexual development in filamentous ascomycete

Wang

Liu

Xiong

et al. 2021

Preprint

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Sexual and asexual reproduction is ubiquitous in eukaryotes. PI3K/AKT signaling pathway can modulate sexual reproduction in mammals. However, this signaling pathway modulating sexual and asexual reproduction in fungi is scarcely understood. SeASF1, a SeH4 chaperone, could manipulate sexual and asexual reproduction of Stemphylium eturmiunum. SeDJ-1, screened from SeΔasf1 transcriptome, was confirmed to regulate sexual and asexual development by RNAi, of which the mechanism was demonstrated by detecting transcriptional levels and protein interactions of SeASF1, SeH4 and SeDJ-1 by qRT-PCR, and Y2H, Co-IP and Pull-down, respectively. SeASF1 coupling SeH4 bound SeDJ-1 to arouse the sexual and asexual activity. In S. eturmiunum genome, SeDJ-1 was upstream while SeGSK3 was downstream in PI3K/AKT signaling pathway. Moreover, SeDJ-1 interacted with SePI3K or SeGSK3 in vivo and in vitro. Significantly, SeDJ-1 or SePI3K could effectively stimulate sexual activity alone, but SePI3K could recover the sexual development of SiSeDJ-1.SeDJ-1-M6 was a critical segment for interaction of SeDJ-1 with SePI3K. SeDJ-1-M6 played a critical role in irritating sexual reproduction in SiSePI3K, which further uncovered the regulated mechanism of SeDJ-1. SeASF1 coupling SeH4 motivates SeDJ-1 to arouse SePI3K involved in sexual reproduction. Thus, SeASF1 can activate PI3K/AKT signaling pathway to regulate sexual and asexual development in filamentous ascomycete.

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Section: Resultsmentioning

confidence: 98%

ASF1 activation PI3K/AKT pathway regulates sexual and asexual development in filamentous ascomycete

Wang

Liu

Xiong

et al. 2021

Preprint

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“…The PI3K/AKT signaling pathway manipulates a variety of biological processes, but these have rarely been reported in plant and fungi development. Previous reports showed that DJ-1 was mainly attributed to activate the PI3K/AKT signaling pathway in animals (Yang et al 2005;Zhang et al 2016). Notably, both PI3K and GSK3 proteins are crucial components in PI3K/AKT signaling pathway (Oh and Mouradian 2017), while the functions of this pathway would be signi cantly altered when DJ-1 perceived these two crucial components (Lee et al 2021;Sitaram et al 2009;Wang et al 2013).…”

Section: Sedj-1 Is Required For Sepi3k To Modulate Asexual and Sexual...mentioning

confidence: 94%

ASF1 regulates asexual and sexual reproduction in Stemphylium eturmiunum by DJ-1 stimulation of PI3K/AKT signaling pathway

Wang

Liu

Xiong

et al. 2023

Preprint

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Most fungi display a mixed mating system with both asexual and sexual reproduction. The timing of the two modes of reproduction must be carefully coordinated through signal perception and coordination in the cell along with chromatin modification. Here, we investigated coordination of reproductive output by investigating the function of the histone chaperone anti-silencing factor 1 (ASF1) in a fungal species amenable to characterization of both asexual and sexual reproduction. We used knockout approach to show that SeASF1 influenced asexual and sexual reproduction in S. eturmiunum. SeASF1-deleted strains failed to produce perithecia, but produce abnormal conidia and showed an irregular distribution of nuclei in mycelium. Transcriptome sequencing was then used to identify genes with altered expression in the SeASF1-deleted strains. The screen identified SeDJ-1 that was strongly regulated by SeASF1. The interaction of SeDJ-1 and SeASF1 was confirmed using Y2H, Co-IP, and pull-down. The phosphatidylinositol 3kinase/protein kinase B (PI3K/AKT) signaling pathway was known to interact with DJ-1 in mammals, and we verified that SePI3K was directly linked to SeDJ-1 and was defined as a coordinator of reproduction. Meanwhile, SeDJ-1 and SePI3K stimulated asexual and sexual activity, respectively, but SePI3K recovered the asexual and sexual development of SeDJ-1 knockout mutants. The SeDJ-1-M6 segment of SeDJ-1 was essential for its interaction with SePI3K and also carried out a critical role in restoring reproduction in the SePI3K knockout mutants, providing a deep understanding of the regulatory mechanism of SeDJ-1 in S. eturmiunum. Summarily, SeASF1 triggers SeDJ-1 to activate SePI3K which is involved in asexual and sexual reproduction in S. eturmiunum. This study revealed that SeASF1 manipulates asexual and sexual reproduction in S. eturmiunum by SeDJ-1 perception of PI3K/AKT signaling pathway. These data highlight the deep similarities in coordinating asexual and sexual processes in both fungi and eukaryotes in general.

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“…All components of DBYW were listed as the following (with Pharmacopoeia and local names) and described previously ( Zhang et al, 2013 , 2016a ): Amur corktree bark ( Phellodendron chinense Cortex ; Huang-Bai) 12 g, Common anemarrhena rhizome ( Anemarrhenae Rhizoma ; Zhi-Mu) 12 g, Prepared rehmannia root ( Radix Rehmanniae Praeparata ; Shu-Di-Huang) 18 g, and Tortoise shell ( Carapax et Plastrum Testudinis ; Gui-Jia) 18 g. All components were obtained from Beijing Tong-Ren-Tang Nature Pharmacy (Beijing, China) and authenticated by the pharmacognosy professionals in the pharmacy. Briefly, the preparation method for the decoction was described previously ( Chan et al, 2012 ).…”

Section: Methodsmentioning

confidence: 99%

Da-Bu-Yin-Wan Improves the Ameliorative Effect of DJ-1 on Mitochondrial Dysfunction Through Augmenting the Akt Phosphorylation in a Cellular Model of Parkinson’s Disease

et al. 2018

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Da-Bu-Yin-Wan (DBYW) is recorded originally in China over six centuries ago, and it is used to treat Parkinson’s disease (PD) clinically in recent decades. DJ-1 is a homodimeric protein linked to early-onset PD, and found in the mitochondria. In addition, DJ-1 could protect the cells by regulating gene transcription and modulating the Akt signal pathways. Therefore, in this research, we aimed to investigate the ameliorative effect of DBYW on mitochondria in the view of the DJ-1 and Akt signaling. Rat adrenal pheochromocytoma cell line PC-12 was transfected with the plasmid pcDNA3-Flag-DJ-1 (pDJ-1). Subsequently, PC-12 cells were exposed to the PD-related mitochondrial toxin (1-methyl-4-phenylpyridinium) without/with the DBYW. After transfected with the plasmid pDJ-1, the 1-methyl-4-phenylpyridinium-induced toxicity was decreased, and the DJ-1 expression in protein level was increased. DJ-1 overexpression not only increased the mitochondrial mass, but also improved the total ATP content. Moreover, Akt phosphorylation was augmented by DJ-1 overexpression. Additionally, DBYW enhanced the above effects. Conclusively, these findings indicate that DBYW promotes the ameliorative effects of DJ-1 on mitochondrial dysfunction at least through augmenting the Akt phosphorylation in 1-methyl-4-phenylpyridinium-treated PC-12 cells.

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Protective effects of DJ-1 medicated Akt phosphorylation on mitochondrial function are promoted by Da-Bu-Yin-Wan in 1-methyl-4-phenylpyridinium-treated human neuroblastoma SH-SY5Y cells

Cited by 14 publications

References 58 publications

ASF1 activation PI3K/AKT pathway regulates sexual and asexual development in filamentous ascomycete

ASF1 activation PI3K/AKT pathway regulates sexual and asexual development in filamentous ascomycete

ASF1 regulates asexual and sexual reproduction in Stemphylium eturmiunum by DJ-1 stimulation of PI3K/AKT signaling pathway

Da-Bu-Yin-Wan Improves the Ameliorative Effect of DJ-1 on Mitochondrial Dysfunction Through Augmenting the Akt Phosphorylation in a Cellular Model of Parkinson’s Disease

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