HDLs extract lipophilic drugs from cells

Zheng, Adi; Dubuis, Gilles; Georgieva, Maria; Ferreira, Carla Susana Mendes; Serulla, Marc; Rubio, Maria del Carmen Conde; Trofimenko, Evgeniya; Mercier, Thomas; Décosterd, Laurent A.; Widmann, Christian

doi:10.1242/jcs.258644

Cited by 4 publications

(4 citation statements)

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“…The specific primers are as follows: ATF3, forward: 5′‐TAG CCC CTG AAG AAG ATG AAA G‐3′ and reverse: 5′‐CTT CTT CTT GTT TCG GCA CTT T‐3′; ATF4, forward: 5′‐ATG GAT TTG AAG GAG TTC GAC T‐3′ and reverse: 5′‐AGA GAT CAC AAG TGT CAT CCA A‐3′; ATF6, forward: 5′‐CTG ATG GCT GTT CAA TAC ACA G‐3′ and reverse: 5′‐GAT CCC TTC GAA ATG ACA CAA C‐3′. The primers of BIP, CHOP and GAPDH used in this study were described previously 28–30 . GAPDH served as control to normalize mRNA expression level.…”

Section: Methodsmentioning

confidence: 99%

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Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF_2α/CHOP axis in oesophageal squamous cell carcinoma

Yuan,

Liu,

Yang

et al. 2023

J Cellular Molecular Medi

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Acetylshikonin (AS) is an active component of Lithospermum erythrorhizon Sieb. et Zucc that exhibits activity against various cancers; however, the underlying mechanisms of AS against oesophageal squamous carcinoma (ESCC) need to be elusive. The research explores the anti‐cancer role and potential mechanism of AS on ESCC in vitro and in vivo, providing evidences for AS treatment against ESCC. In this study, we firstly demonstrated that AS treatment effectively inhibits cell viability and proliferation of ESCC cells. In addition, AS significantly induces G1/S phage arrest and promotes apoptosis in ESCC cell lines. Further studies reveal that AS induces ER stress, as observed by dose‐ and time‐dependently increased expression of BIP, PDI, PERK, phosphorylation of eIF2α, CHOP and splicing of XBP1. CHOP knockdown or PERK inhibition markedly rescue cell apoptosis induced by AS. Moreover, AS treatment significantly inhibits ESCC xenograft growth in nude mice. Elevated expression of BIP and CHOP is also observed in xenograft tumours. Taken together, AS inhibits proliferation and induces apoptosis through ER stress‐activated PERK/eIF2α/CHOP pathway in ESCC, which indicates AS represents a promising candidate for ESCC treatment.

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Section: Methodsmentioning

confidence: 99%

“…The primers of BIP, CHOP and GAPDH used in this study were described previously. 28 , 29 , 30 GAPDH served as control to normalize mRNA expression level.…”

Section: Methodsmentioning

confidence: 99%

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF_2α/CHOP axis in oesophageal squamous cell carcinoma

Yuan,

Liu,

Yang

et al. 2023

J Cellular Molecular Medi

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“…Consequently, the lipoprotein-mediated drug transport is a potential contributor to the transport and metabolism of lipophilic drugs in the body, the role of which should be considered when developing new pharmacotherapies [24]. In line with this, the evidence of the lipoprotein transport of fat-soluble xenobiotics would mean that lipoproteins are involved in the distribution and toxic effects of these chemicals in the body [26].…”

Section: Transport Of Lipophilic Substances Other Than Plasma Lipidsmentioning

confidence: 98%

“…A recent study showed that HDLs can utilize their capacity of loading themselves with lipophilic compounds, similarly to their ability to extract cellular cholesterol, to reduce the cell content of lipophilic drugs and xenobiotics. ABC transporters were not required for the process, but however, could favor it [26].…”

Section: Experimental Evidence Of the Role Of Hdlmentioning

confidence: 99%

Lipid Oxidation Products and the Risk of Cardiovascular Diseases: Role of Lipoprotein Transport

Ahotupa

2024

Antioxidants

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Cholesterol has for decades ruled the history of atherosclerotic cardiovascular diseases (CVDs), and the present view of the etiology of the disease is based on the transport of cholesterol by plasma lipoproteins. The new knowledge of the lipoprotein-specific transport of lipid oxidation products (LOPs) has introduced another direction to the research of CVD, revealing strong associations between lipoprotein transport functions, atherogenic LOP, and CVD. The aim of this review is to present the evidence of the lipoprotein-specific transport of LOP and to evaluate the potential consequences of the proposed role of the LOP transport as a risk factor. The associations of cholesterol and lipoprotein LOP with the known risk factors of CVD are mostly parallel, and because of the common transport and cellular intake mechanisms it is difficult to ascertain the independent effects of either cholesterol or LOP. While cholesterol is known to have important physiological functions, LOPs are merely regarded as metabolic residues and able to initiate and boost atherogenic processes. It is therefore likely that with the increased knowledge of the lipoprotein-specific transport of LOP, the role of cholesterol as a risk factor of CVD will be challenged.

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High-density lipoprotein revisited: biological functions and clinical relevance

Eckardstein

Nordestgaard

Remaley

et al. 2022

European Heart Journal

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Previous interest in high-density lipoproteins (HDLs) focused on their possible protective role in atherosclerotic cardiovascular disease (ASCVD). Evidence from genetic studies and randomized trials, however, questioned that the inverse association of HDL-cholesterol (HDL-C) is causal. This review aims to provide an update on the role of HDL in health and disease, also beyond ASCVD. Through evolution from invertebrates, HDLs are the principal lipoproteins, while apolipoprotein B-containing lipoproteins first developed in vertebrates. HDLs transport cholesterol and other lipids between different cells like a reusable ferry, but serve many other functions including communication with cells and the inactivation of biohazards like bacterial lipopolysaccharides. These functions are exerted by entire HDL particles or distinct proteins or lipids carried by HDL rather than by its cholesterol cargo measured as HDL-C. Neither does HDL-C measurement reflect the efficiency of reverse cholesterol transport. Recent studies indicate that functional measures of HDL, notably cholesterol efflux capacity, numbers of HDL particles, or distinct HDL proteins are better predictors of ASCVD events than HDL-C. Low HDL-C levels are related observationally, but also genetically, to increased risks of infectious diseases, death during sepsis, diabetes mellitus, and chronic kidney disease. Additional, but only observational, data indicate associations of low HDL-C with various autoimmune diseases, and cancers, as well as all-cause mortality. Conversely, extremely high HDL-C levels are associated with an increased risk of age-related macular degeneration (also genetically), infectious disease, and all-cause mortality. HDL encompasses dynamic multimolecular and multifunctional lipoproteins that likely emerged during evolution to serve several physiological roles and prevent or heal pathologies beyond ASCVD. For any clinical exploitation of HDL, the indirect marker HDL-C must be replaced by direct biomarkers reflecting the causal role of HDL in the respective disease.

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HDLs extract lipophilic drugs from cells

Cited by 4 publications

References 50 publications

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF_2α/CHOP axis in oesophageal squamous cell carcinoma

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF_2α/CHOP axis in oesophageal squamous cell carcinoma

Lipid Oxidation Products and the Risk of Cardiovascular Diseases: Role of Lipoprotein Transport

High-density lipoprotein revisited: biological functions and clinical relevance

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HDLs extract lipophilic drugs from cells

Cited by 4 publications

References 50 publications

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF2α/CHOP axis in oesophageal squamous cell carcinoma

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF2α/CHOP axis in oesophageal squamous cell carcinoma

Lipid Oxidation Products and the Risk of Cardiovascular Diseases: Role of Lipoprotein Transport

High-density lipoprotein revisited: biological functions and clinical relevance

Contact Info

Product

Resources

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Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF_2α/CHOP axis in oesophageal squamous cell carcinoma

Acetylshikonin induces apoptosis through the endoplasmic reticulum stress‐activated PERK/eIF_2α/CHOP axis in oesophageal squamous cell carcinoma