Oxidized Low-density Lipoprotein Upregulates GM2 Activator Protein Gene Expression

Yanai, Hidekatsu; Yoshida, Hiroshi; Fujiwara, Hironobu; Yoshida, Shigeru; Fuda, Hirotoshi; Hui, Shu‐Ping; Nagasaka, Hironori; Tada, Norio; Chiba, Hitoshi

doi:10.3844/ajbbsp.2005.90.94

Cited by 3 publications

(2 citation statements)

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“…METH toxicity is frequently reported as a potential model of drug induced Parkinsonism, which is one of the most common movement disorders of the elderly. Chronic or intermittent METH abuse may create temporary or permanent disturbances in the dopaminergic systems of the brain that may predispose individuals to Parkinsonism (Kita et al, 2003;Fisher et al, 2005;Yanai et al, 2005;Tolwani et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Zhou¹

2010

American Journal of Pharmacology and Toxicology

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Problem statement: Sulfotransferases (SULTs) are important phase II drug metabolizing enzymes. They also regulate the biological activities of various hormones. To the best of our knowledge, psychostimulants regulation of SULTs is basically not studied except one article reported that Methamphetamine (METH) treatment induced rat amygdale rSULT1A1 mRNA 4.3 fold by using microarray method to identify a series of candidate genes after single-dose METH treatment. The psychostimulant METH is used to treat disorders such as attention deficit, narcolepsy and obesity. It is also a highly addictive drug that causes serious social problems. The abuse of this drug leads to the damage of monoaminergic systems in the mammalian brain. It is important to understand how SULT expressions are regulated by psychostimulants. Approach: This study was performed to evaluate the effect of METH on SULT gene expressions in rat liver and brain. METH (0, 1, 5, 20 mg kg −1 day −1 ) was used to treat male and female rats for 7 days by oral administration. Rat livers and brains were collected 24 h after the final drug treatment. Western blot and real-time RT-PCR were used to investigate the effect of METH on SULT protein and mRNA expression, respectively, in rat liver and brain. Results: Proteins and mRNAs of rSULT1A1, rSULT2A1 and rSULT1E1 were induced in liver and brain of both male and female rats following METH treatment. rSULT1E1 was induced at much higher level compared to that of rSULT1A1 and rSULT2A1. Brain inductions were found to be much higher than those found in liver. Conclusion: These data suggest an important role of the central dopaminergic system in the regulation of liver and brain rSULT expressions.

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Section: Introductionmentioning

confidence: 99%

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Zhou¹

2010

American Journal of Pharmacology and Toxicology

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“…Up‐regulated Cer and GM2 were strongly associated with AS (Gouni‐Berthold et al, 2001; Panagiotis et al, 2015; Yu et al, 2015). It is reported that GM2 ganglioside activator protein is a general lipid transporter in macrophages, which is regulated by ox‐LDL and subsequently enhances glycosphingolipid accumulation (Yanai, 2005; Yanai et al, 2006). Cer, as the second messengers of cells and the metabolic hub of sphingolipid, produced a variety of biological effects in the cardiovascular system: inducing apoptosis of smooth muscle and myocardial cells, regulating immune function and inflammatory response, participating in oxidative stress, etc.…”

Section: Discussionmentioning

confidence: 99%

Lipidomics reveals the dysregulated ceramide metabolism in oxidized low‐density lipoprotein‐induced macrophage‐derived foam cell

Liu

Pei

et al. 2021

Biomedical Chromatography

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Atherosclerosis (AS) is associated with increasing lipid peroxidation. Oxidative modification of low-density lipoproteins (ox-LDL) is one most important factors contributing to the pathogenesis and clinical features of AS. The lipid composition influenced by ox-LDL is not known clearly. In this work, a UHPLC/Orbitrap MS-based lipidomics approach integrated pathway analysis was performed to advance understanding of the lipid composition and feature pathway in an ox-LDL-induced foamy macrophage cell. In the lipid metabolic profiling, 196 lipid species from 15 (sub)classes were identified. Lipid profiling indicated that increasing ox-LDL caused lipid metabolic alternations, manifesting as phospholipids being down-regulated and sphingolipids being up-regulated. Pathway analysis explored glycerophospholipid and sphingolipid metabolism, which was involved in atherogenic changes. Notably, dysregulated ceramide metabolism was a typical feature of foamy cell formation. qRT-PCR analysis was conducted to explore the differentially expressed genes. It indicated that ceramide metabolic balance might be disordered, performing higher synthesis and lower hydrolysis, with the ratio of SMPD1/SGMS2 being significantly up-regulated (p < 0.05) in the ox-LDL induced group. Our work offers a comprehensive understanding of macrophage-derived foam cells and screen feature pathways associated with foamy cell formation, which provides a reference for the clinic diagnosis of AS and drug interventions.

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