Astaxanthin from <i>Haematococcus pluvialis</i> ameliorates the chemotherapeutic drug (doxorubicin) induced liver injury through the Keap1/Nrf2/HO-1 pathway in mice

Ma, Haotian; Chen, Shuaihang; Xiong, Huaye; Wang, Meng; Wei, Hang; Zhu, Xiaoli; Zheng, Yubing; Ge, Baosheng; Li, Runzhi; Cui, Hongli

doi:10.1039/c9fo02429h

Cited by 46 publications

(32 citation statements)

References 54 publications

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“…The chemopreventive potential of AX was found to be prominent in hamster buccal pouch carcinoma, where it suppressed JAK2/STAT3 signaling, particularly the phosphorylation and consequent nuclear translocation of STAT3 [288]. Doxorubicinand ochratoxin-induced liver injury was improved by AX through activating Nrf2, degrading Keap1, and upregulating HO-1 and Mn-SOD expressions [289,290]. Here, ERK level was increased and NF-κB level was decreased by AX.…”

Section: Astaxanthin (Ax)mentioning

confidence: 95%

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

et al. 2021

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ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.

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Section: Astaxanthin (Ax)mentioning

confidence: 95%

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

et al. 2021

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“…Triacylglycerol (TAG) is the principal energy storage form in eukaryotic organisms and represents a promising source of biodiesel production [1]. Microalgae can efficiently absorb CO 2 in the atmosphere and turn it into abundant high-value products, including polysaccharides, lipids, proteins, pigments, and biofuels [2][3][4][5]. Due to their high photosynthetic efficiency, rapid reproduction rate, and short growth cycle, microalgae have been considered as the best candidates to resolve energy crises and environmental pollution [6].…”

Section: Introductionmentioning

confidence: 99%

Characterization of type-2 diacylglycerol acyltransferases in Haematococcus lacustris reveals their functions and engineering potential in triacylglycerol biosynthesis

Cui

Zhao

et al. 2021

BMC Plant Biol

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Background Haematococcus lacustris is an ideal source of astaxanthin (AST), which is stored in oil bodies containing esterified AST (EAST) and triacylglycerol (TAG). Diacylglycerol acyltransferases (DGATs) catalyze the last step of acyl-CoA-dependent TAG biosynthesis and are also considered as crucial enzymes involved in EAST biosynthesis in H. lacustris. Previous studies have identified four putative DGAT2-encoding genes in H. lacustris, and only HpDGAT2D allowed the recovery of TAG biosynthesis, but the engineering potential of HpDGAT2s in TAG biosynthesis remains ambiguous. Results Five putative DGAT2 genes (HpDGAT2A, HpDGAT2B, HpDGAT2C, HpDGAT2D, and HpDGAT2E) were identified in H. lacustris. Transcription analysis showed that the expression levels of the HpDGAT2A, HpDGAT2D, and HpDGAT2E genes markedly increased under high light and nitrogen deficient conditions with distinct patterns, which led to significant TAG and EAST accumulation. Functional complementation demonstrated that HpDGAT2A, HpDGAT2B, HpDGAT2D, and HpDGAT2E had the capacity to restore TAG synthesis in a TAG-deficient yeast strain (H1246) showing a large difference in enzymatic activity. Fatty acid (FA) profile assays revealed that HpDGAT2A, HpDGAT2D, and HpDGAT2E, but not HpDGAT2B, preferred monounsaturated fatty acyl-CoAs (MUFAs) for TAG synthesis in yeast cells, and showed a preference for polyunsaturated fatty acyl-CoAs (PUFAs) based on their feeding strategy. The heterologous expression of HpDGAT2D in Arabidopsis thaliana and Chlamydomonas reinhardtii significantly increased the TAG content and obviously promoted the MUFAs and PUFAs contents. Conclusions Our study represents systematic work on the characterization of HpDGAT2s by integrating expression patterns, AST/TAG accumulation, functional complementation, and heterologous expression in yeast, plants, and algae. These results (1) update the gene models of HpDGAT2s, (2) prove the TAG biosynthesis capacity of HpDGAT2s, (3) show the strong preference for MUFAs and PUFAs, and (4) offer target genes to modulate TAG biosynthesis by using genetic engineering methods.

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“…Triacylglycerol (TAG) is the principal storage form of energy in eukaryotic organisms and represents a promising source of biodiesel production [1]. Microalgae can e ciently absorb CO 2 in the atmosphere and turn it into abundant high value products including polysaccharide, lipid, protein, pigment, and biofuel [2][3][4][5]. Due to high photosynthetic e ciency, rapid reproduction rate, and short growth cycle, microalgae have been considered as the best candidate to resolve energy crisis and environmental pollution [6].…”

Section: Introductionmentioning

confidence: 99%

Characterization of type-2 diacylglycerol acyltransferases in Haematococcus lacustris reveals their functions and engineering potential in triacylglycerol biosynthesis and possible roles in astaxanthin esterification

Cui

Zhao

et al. 2020

Preprint

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Background: Haematococcus lacustris is an ideal source of astaxanthin (AST) which is stored at oil bodies containing esterified AST (EAST) and triacylglycerol (TAG). Diacylglycerol acyltransferases (DGATs) catalyze the last step of the acyl-CoA-dependent TAG biosynthesis and are also considered as the crucial enzymes involving in EAST biosynthesis in H. lacustris. Previous studies have identified four putative DGAT2 encoding genes in H. lacustris and only the HpDGAT2D allowed the recovery of TAG biosynthesis, but the engineering potential of HpDGAT2s in TAG biosynthesis, especially possible roles in AST esterification, remains ambiguous.Results: Five putative DGAT2 genes (HpDGAT2A, HpDGAT2B, HpDGAT2C, HpDGAT2D, and HpDGAT2E) were identified in H. lacustris. Transcription analysis showed that the expression levels of HpDGAT2A, HpDGAT2D, and HpDGAT2E genes markedly increased under high light and nitrogen deficient conditions with distinct patterns, which led to significant TAG and EAST accumulation. Functional complementation demonstrated HpDGAT2A, HpDGAT2B, HpDGAT2D, and HpDGAT2E had the capability to restore TAG synthesis in a TAG-deficient yeast strain (H1246) with the large difference in enzymatic activity. Fatty acids (FAs) profiles assays revealed that HpDGAT2A, HpDGAT2D, and HpDGAT2E except for HpDGAT2B preferred monounsaturated fatty acyl-CoAs (MUFAs) for TAG synthesis in yeast cells, and also showed polyunsaturated fatty acyl-CoAs (PUFAs) preference by feeding strategy. The over-expression of HpDGAT2D in Arabidopsis thaliana and Chlamydomonas reinhardtii significantly increased the TAG content and obviously promoted the MUFAs and PUFAs contents. Interestingly, molecular docking analysis implied that HpDGAT2s structures contained AST binding sites, which provides strong evidence for AST esterification function in H. lacustris.Conclusions: Our study represents a pioneering work on the characterization of HpDGAT2s by systematically integrating expression pattern, AST/TAG accumulation, functional complementation, molecular docking, and over-expression in yeast, plants, and algae. These results (1) update the gene models of HpDGAT2s, (2) prove TAG biosynthesis capacity of HpDGAT2s, (3) show the strong preference for MUFAs and PUFAs, (4) offer target genes to modulate TAG biosynthesis by genetic engineering method, and (5) provide new evidence for HpDGAT2s roles in AST esterification.

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Astaxanthin from Haematococcus pluvialis ameliorates the chemotherapeutic drug (doxorubicin) induced liver injury through the Keap1/Nrf2/HO-1 pathway in mice

Abstract: The aim of this study is to probe a new function of astaxanthin (AST) from Haematococcus pluvialis on chemotherapeutic drug (doxorubicin) induced liver injury in mice.

Cited by 46 publications

References 54 publications

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

Characterization of type-2 diacylglycerol acyltransferases in Haematococcus lacustris reveals their functions and engineering potential in triacylglycerol biosynthesis

Characterization of type-2 diacylglycerol acyltransferases in Haematococcus lacustris reveals their functions and engineering potential in triacylglycerol biosynthesis and possible roles in astaxanthin esterification

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