Lupeol against high-glucose-induced apoptosis via enhancing the anti-oxidative stress in rabbit nucleus pulposus cells

Guo, Mingbo; Wang, Dechun; Liu, Haifei; Chen, Longwei; Wei, Jianwei; Lin, Yu-Chuan; Xue, Hui

doi:10.1007/s00586-018-5687-9

Cited by 16 publications

(19 citation statements)

References 40 publications

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“…In addition, our results also showed a positive dose-effect relationship between glucose concentration and AF cell apoptosis. In line with us, several studies also showed that high glucose promotes disc cell apoptosis, such as CEP cells and notochordal cells [20,21]. Hence, inhibiting high glucose-induced disc cell apoptosis may be an effective strategy to retard disc degeneration in DM patients.…”

Section: Discussionsupporting

confidence: 65%

“…Recently, some epidemiological studies have demonstrated that diabetes facilitates disc degeneration, and DM patients have a higher incidence of disc degeneration than non-DM patients [3,[27][28][29]. Several basic researches have investigated the responses of disc cells to high glucose treatment and reported that high glucose significantly promotes senescence of disc NP cells, notochordal cells and AF cells [17][18][19], and induces apoptosis of disc CEP cells and notochordal cells [20,21]. However, the effects of high glucose on AF cell apoptosis are unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, some studies have reported that a high glucose environment significantly promotes senescence of disc NP cells, notochordal cells and AF cells [17][18][19]. Moreover, several studies have showed that a high glucose environment induces apoptosis of disc CEP cells and notochordal cells [20,21]. However, few studies have observed the effects of a high glucose environment on disc AF cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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“…Lupeol, a pentacyclic triterpene, is an important intermediate metabolite from the conversion of 2,3oxidosqualene to a series of lupane-type triterpenoids and has attracted increasing attention due to its anti-HIV, anticancer and anti-in ammatory activities [3,29,30]. To produce lupeol from acetyl-CoA through the MVA pathway in Y. lipolytica, we assembled the following heterologous genes encoding lupeol synthases from different sources in strain ATCC 201249: AtLus from Arabidopsis thaliana, GuLus from Glycyrrhiza uralensis, OeLus from Olea europaea, BgLus from Bruguiera gymnorhiza, KdLus from Kalanchoe daigremontiana and RcLus from Ricinus communis.…”

Section: Establishment Of Lupeol Synthesis In Y Lipolyticamentioning

confidence: 99%

“…Nevertheless, terpenoids, known for their in vivo antifungal activity, are generally highly toxic to microorganisms, inducing apoptosis and having a negative impact on terpene production [3][4][5][6][7][8]. For instance, lupeol, a typical triterpenoid, caused severe damage to cell viability even at a relatively low concentration of 60 mg/L [3,8]. To decrease the intractable cytotoxicity, extensive efforts aimed at creating oleaginous subcellular organelles by altering lipid-droplet composition and size potentially improved the terpene partition coe cient in oil droplets and the storage space so that lipophilic terpenes can accumulate in these compartments [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components

Zhang

Bai

Peng

et al. 2020

Preprint

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Background Lupeol exhibits novel physiological and pharmacological activities, such as anticancer and immunity-enhancing activities. However, cytotoxicity remains a challenge for triterpenoid overproduction in microbial cell factories. As lipophilic and relatively small-molecular compounds, triterpenes are generally secreted into the extracellular space. The effect of increasing triterpene efflux on the synthesis capacity remains unknown.Results In this study, we developed a strategy to enhance triterpene efflux through manipulation of lipid components in Y. lipolytica by overexpressing the enzyme Δ9-fatty acid desaturase (OLE1) and disturbing phosphatidic acid phosphatase (PAH1) and diacylglycerol kinase (DGK1). By this strategy combined with two-phase fermentation, the highest lupeol production reported to date was achieved, where the titer in the organic phase reached 381.67 mg/L and the total production was 411.72 mg/L in shake flasks, exhibiting a 33.20-fold improvement over the initial strain. Lipid manipulation led to a two-fold increase in the unsaturated fatty acid (UFA) content, up to 61%~73%, and an exceptionally elongated cell morphology, which might have been caused by enhanced membrane phospholipid biosynthesis flux. Both phenotypes accelerated the export of toxic products to the extracellular space and ultimately stimulated the capacity for triterpenoid synthesis, which was proven by the 5.11-fold higher ratio of extra/intracellular lupeol concentrations, 2.79-fold higher biomass accumulation and 2.56-fold higher lupeol productivity per unit OD in the modified strains. This strategy was also highly efficient for the biosynthesis of other triterpenes and sesquiterpenes, including α-amyrin, β-amyrin, longifolene, longipinene and longicyclene.Conclusions In conclusion, we successfully created a high-yield lupeol-producing strain via lipid manipulation. We demonstrated that the enhancement of lupeol efflux and synthesis capacity was induced by the increased UFA content and elongated cell morphology. Our study provides a novel strategy to promote the biosynthesis of valuable but toxic products in microbial cell factories.

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Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation

Zhang

Hao

et al. 2020

Metab Brain Dis

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Lupeol against high-glucose-induced apoptosis via enhancing the anti-oxidative stress in rabbit nucleus pulposus cells

Cited by 16 publications

References 40 publications

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components

Beneficial consequences of Lupeol on middle cerebral artery-induced cerebral ischemia in the rat involves Nrf2 and P38 MAPK modulation

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