Control of apolipoprotein E secretion in the human hepatoma cell line KYN‐2

Abstract

Even though it is known that apolipoprotein E (apoE) is deeply involved in major age-related disorders such as atherosclerosis or Alzheimer's disease (AD), the control of cell-specific apoE expression is still poorly understood. We compared the apoE secretion as previously described in astrocytic cell17 to hepatic cell apoE secretion. We used the human hepatoma cell line KYN-2 to better delineate the characteristics of apoE secretion and to validate it with respect to the classical human hepatoma cell line HepG2. Interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) significantly inhibited, while IL-2, IL-6 and tumour necrosis factor-alpha (TNF-alpha) were inactive on apoE secretion by KYN-2 as well as HepG2 cells. Cholesterol and 25-OH cholesterol had no effect, while forskolin exerted a significant inhibitory effect, on apoE secretion in KYN-2 cells. Our results suggest that the KYN-2 cell line represents an appropriate cell model, and in any case an alternative model to the HepG2 cell line, to study the control of apoE secretion. The response of KYN-2 cells to both cytokines and cholesterol differs from that found in astrocytoma cells, suggesting that blood variations of apoE concentrations in AD may not reflect the dysregulations taking place in the brain.

Genetic profiling of human cell lines used as in vitro model to study cardiovascular pathophysiology and pharmacotoxicology

“…Cellular models are widely used to study gene expression profiling. For example, it was shown that Kyn2 and HepG2 cells express active peroxisome proliferator-activated receptor gamma (Rumi et al 2001) and apolipoprotein E (Brahimi et al 2001). Studies have been interested into cell line genetic profiles in order to correlate them with expression of diverse phenotypes.…”

“…They permit biochemical characterization of a number of pathways, in conditions resembling physiologic or pathologic conditions (Brahimi et al 2001;Fach et al 2004;Riou et al 2007). Cell lines also help to study a response to drugs by providing information on their efficacy, toxicity, and mechanisms of action.…”

“…On the other hand, myeloid leukemia cell lines, HL60 and K562, are used to determine expression profile of drug metabolizing enzymes in human blood cells (Nagai et al 2002). Hepatic HepG2 and Kyn2 cells are also utilized to study lipid metabolism and drugs effect (Brahimi et al 2001;Maejima et al 2004;Brandon et al 2006). Regarding Caco2 cell line, it has been shown to be useful model to study metabolism and transport of a number of drugs (Brandon et al 2006).…”

Protein level of apolipoprotein E increased in human hepatocellular carcinoma

“…It has been reported that the inhibition of VLDL secretion by HCV core protein or a mutation of apoE causes apoE to accumulate in HCC tissues. ApoE is produced and secreted by human hepatoma cell lines (32,33) as well as by fetal liver (27), and the expression of apoE increases during embryonic development in zebrafish (34). Moreover, oxidative stress in HCC tissues (35) causes high levels of apoE expression because apoE functions as an anti-oxidant, and apoE mRNA expression increases in prostate cancers with high malignant potential (20), in gastric (21) and ovarian cancers (22).…”

On the role of 25-hydroxycholesterol synthesis by glioblastoma cell lines. Implications for chemotactic monocyte recruitment

“…This oxysterol affects expression of the cholesterol efflux pumps ATP-binding cassette transporter (ABC)A1 [9] and ABCG1, and expression of apolipoprotein E [10–12]. 25-OHC is able to stimulate LXR-independent oligodendrocyte apoptosis and suppresses myelin gene expression in peripheral nerves via LXR/Wnt/β-catenin-mediated pathways [13].…”