scholarly journals LACCASE is Necessary for Root Development in Salvia miltiorrhiza

2020 ◽  
Author(s):  
Zheng Zhou ◽  
Qing Li ◽  
Yun Wang ◽  
Liang Xiao ◽  
Qitao Bu ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Root Development ◽  
Phenolic Acid ◽  
Gene Locus ◽  
Salvia Miltiorrhiza ◽  
Disease Treatment ◽  
Knock Out ◽  
Laccase Genes ◽  
Mutant Lines ◽  
Acid Compound

AbstractLaccases are multicopper-containing glycoproteins related to monolignol oxidation and polymerization. These properties indicate that laccases are involved in the formation of important medicinal phenolic acid compounds in Salvia miltiorrhiza such as salvianolic acid B (SAB), which is used for cardiovascular disease treatment. To date, 29 laccases have been found in S. miltiorrhiza, some of which influence the synthesis of phenolic acids. Because of the functional redundancy of laccase genes, their roles in S. miltiorrhiza are poorly understood. In this study, the CRISPR/Cas9 system was first used for dual gene locus targeting in S. miltiorrhiza to knock out multiple laccase family genes. The development of the roots was retarded, and root microstructure was abnormal in laccase mutant lines. Additionally, the accumulation of phenolic acid compounds as well as lignin was dramatically reduced. This study suggests that SmLACs are necessary for root development and phenolic acid compound metabolism in S. miltiorrhiza.

scholarly journals Multiplexed CRISPR/Cas9-Mediated Knockout of Laccase Genes in Salvia miltiorrhiza Revealed Their Roles in Growth, Development, and Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Zheng Zhou ◽  
Qing Li ◽  
Liang Xiao ◽  
Yun Wang ◽  
Jingxian Feng ◽  
...  
Keyword(s):  
Phenolic Acids ◽  
Hairy Roots ◽  
Cross Sections ◽  
Phenolic Acid ◽  
Lignin Content ◽  
Salvia Miltiorrhiza ◽  
Acid Biosynthesis ◽  
Disease Treatment ◽  
In The Wild ◽  
Laccase Genes

Laccases are multicopper-containing glycoproteins related to monolignol oxidation and polymerization. These properties indicate that laccases may be involved in the formation of important medicinal phenolic acid compounds in Salvia miltiorrhiza such as salvianolic acid B (SAB), which is used for cardiovascular disease treatment. To date, 29 laccases have been found in S. miltiorrhiza (SmLACs), and some of which (SmLAC7 and SmLAC20) have been reported to influence the synthesis of phenolic acids. Because of the functional redundancy of laccase genes, their roles in S. miltiorrhiza are poorly understood. In this study, the CRISPR/Cas9 system was used for targeting conserved domains to knockout multiple genes of laccase family in S. miltiorrhiza. The expressions of target laccase genes as well as the phenolic acid biosynthesis key genes decrease dramatically in editing lines. Additionally, the growth and development of hairy roots was significantly retarded in the gene-edited lines. The cross-sections examination of laccase mutant hairy roots showed that the root development was abnormal and the xylem cells in the edited lines became larger and looser than those in the wild type. Additionally, the accumulation of RA as well as SAB was decreased, and the lignin content was nearly undetectable. It suggested that SmLACs play key roles in development and lignin formation in the root of S. miltiorrhiza and they are necessary for phenolic acids biosynthesis.

scholarly journals Research advances in kinase enzymes and inhibitors for cardiovascular disease treatment

2017 ◽  
Vol 3 (4) ◽  
pp. FSO204 ◽  
Author(s):  
Rand Shahin ◽  
Omar Shaheen ◽  
Faris El-Dahiyat ◽  
Maha Habash ◽  
Sana Saffour
Keyword(s):  
Cardiovascular Disease ◽  
Disease Treatment

The use of terpenes and derivatives as a new perspective for cardiovascular disease treatment: a patent review (2008–2018)

2018 ◽  
Vol 29 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Eric Aian P. Silva ◽  
Jéssica S. Carvalho ◽  
Adriana G. Guimarães ◽  
Rosana de S.S. Barreto ◽  
Márcio R.V. Santos ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Disease Treatment ◽  
Patent Review ◽  
New Perspective

The promotion effect of phenolic acid compound on the photo-removal of estrogen from water under simulated sunlight irradiation

2020 ◽  
Vol 387 ◽  
pp. 123999
Author(s):  
Mengjie Wang ◽  
Qinren Shi ◽  
Huanhuan Shi ◽  
Jianhua Li ◽  
Yun Yang ◽  
...  
Keyword(s):  
Phenolic Acid ◽  
Simulated Sunlight ◽  
Sunlight Irradiation ◽  
Promotion Effect ◽  
Acid Compound

scholarly journals Cardiovascular Issues Among Homeless People: An Issue that Needs Attention

2020 ◽  
Vol 14 ◽  
pp. 117954682097503
Author(s):  
Muhammad Haisum Maqsood ◽  
Omer Kamal ◽  
David Charytan
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Delayed Diagnosis ◽  
Homeless People ◽  
Treatment Access ◽  
Disease Treatment ◽  
Future Directions ◽  
Cardiovascular Prognosis ◽  
High Prevalence ◽  
Common Causes

Cardiovascular disease is one of the most common causes of death with social factors increasingly recognized as determinants of cardiovascular prognosis. Homelessness, transient or chronic, may be one of the factors which predict treatment access and eventual outcomes as socially and economically disadvantaged group has high prevalence of cardiovascular risk factors such as smoking, and delayed diagnosis and poor control of other risk factors such as diabetes and hypertension. This perspective article aims to discuss the issues associated with cardiovascular disease treatment, outcomes and future directions for homeless patients.

Improved phenolic acid content and bioactivities of Salvia miltiorrhiza hairy roots by genetic manipulation of RAS and CYP98A14

2020 ◽  
Vol 331 ◽  
pp. 127365 ◽  
Author(s):  
Rong Fu ◽  
Min Shi ◽  
Changping Deng ◽  
Yi Zhang ◽  
Xichen Zhang ◽  
...  
Keyword(s):  
Hairy Roots ◽  
Phenolic Acid ◽  
Acid Content ◽  
Genetic Manipulation ◽  
Salvia Miltiorrhiza

scholarly journals The glycosyltransferase UGT76B1 is critical for plant immunity as it governs the homeostasis of N-hydroxy-pipecolic acid

2020 ◽  
Author(s):  
Lennart Mohnike ◽  
Dmitrij Rekhter ◽  
Weijie Huang ◽  
Kirstin Feussner ◽  
Hainan Tian ◽  
...  
Keyword(s):  
Systemic Acquired Resistance ◽  
Plant Immunity ◽  
Acquired Resistance ◽  
Pipecolic Acid ◽  
Balance Growth ◽  
Loss Of Function ◽  
Long Distance ◽  
Knock Out ◽  
Endogenous Substrates ◽  
Mutant Lines

AbstractThe trade-off between growth and defense is a critical aspect of plant immunity. Therefore, plant immune response needs to be tightly regulated. The hormone regulating plant defense against biotrophic pathogens is salicylic acid (SA). Recently, N-hydroxy-pipecolic acid (NHP) was identified as second regulator for plant innate immunity and systemic acquired resistance. Although the biosynthetic pathway leading to NHP formation has already been identified, the route how NHP is further metabolized was unclear. Here, we present UGT76B1 as a UDP-dependent glycosyltransferase that modifies NHP by catalyzing the formation of 1-O-glucosyl-pipecolic acid (NHP-OGlc). Analysis of T-DNA and CRISPR knock-out mutant lines of UGT76B1 by targeted and non-targeted UHPLC-HRMS underlined NHP and SA as endogenous substrates of this enzyme in response to Pseudomonas infection and UV treatment. UGT76B1 shows similar KM for NHP and SA. ugt76b1 mutant plants have a dwarf phenotype and a constitutive defense response which can be suppressed by loss of function of the NHP biosynthetic enzyme FMO1. This suggests that elevated accumulation of NHP contributes to the enhanced disease resistance in ugt76b1. Externally applied NHP can move to distal tissue in ugt76b1 mutant plants. Although glycosylation is not required for the long distance movement of NHP during systemic acquired resistance, it is crucial to balance growth and defense.

scholarly journals The P387 Thrombospondin-4 Variant Promotes Accumulation of Macrophages in Atherosclerotic Lesions

2019 ◽  
Author(s):  
Santoshi Muppala ◽  
Mohammed Tanjimur Rahman ◽  
Irene Krukovets ◽  
Dmitriy Verbovetskiy ◽  
Elzbieta Pluskota ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Smooth Muscle Actin ◽  
Vascular Inflammation ◽  
Cutting Temperature ◽  
Vascular Wall ◽  
Alpha Smooth Muscle Actin ◽  
Knock Out ◽  
Atherosclerotic Lesions ◽  
Thrombospondin 4

AbstractAimsThrombopspondin-4 (TSP4) is a pro-angiogenic protein that has been implicated in tissue remodeling and local vascular inflammation. TSP4 and, in particular, its SNP variant, P387 TSP4, have been associated with cardiovascular disease.Macrophages are central to initiation and resolution of inflammation and development of atherosclerotic lesions, but the effects of the P387 TSP4 on macrophages remain essentially unknown. We examined the effects of the P387 TSP4 variant on macrophages in cell culture andin vivoin a murine model of atherosclerosis. Further, the levels and distributions of the twoTSP4 variants were assessed in human atherosclerotic arteries.Methods and ResultsInApoE−/−/P387-TSP4 knock-in mice, atherosclerotic lesions accumulated more macrophages than lesions bearing A387 TSP4. The levels of inflammatory markers were increased in lesions ofApoE−/−/P387-TSP4 knock-in mice compared toApoE−/−mice. Lesions in human arteries from individuals carrying the P387 variant had higher levels of TSP4 and higher macrophage accumulation. P387 TSP4 was more active in supporting adhesion of cultured human and mouse macrophages in experiments using recombinant TSP4 variants and in cells derived from P387-TSP4 knock-in mice.ConclusionsTSP4 supports the adhesion of macrophages and their accumulation in atherosclerotic lesions. P387 TSP4 is more active in supporting these pro-inflammatory events in the vascular wall, which may contribute to the increased association of P387 TSP4 with cardiovascular disease.AbbreviationsBSA, bovine serum albumin; DMSO, dimethyl sulfoxide; ECM, extracellular matrix;Thbs4−/−, thrombospondin-4 gene knock-out; WT, wild type; P387-TSP4 KI, P387TSP4knock-in mice; OCT, Optimum Cutting Temperature; vWF, von Willebrand factor; α-SMA, alpha-smooth muscle actin; Egr2, Early Growth Response 2; PBS, Phosphate Buffer saline; DMEM, Dulbecco’s Modified Eagle Medium.

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