Overexpression of STARD3 attenuates oxidized LDL-induced oxidative stress and inflammation in retinal pigment epithelial cells

Almarhoun, Mohammad; Biswas, Lincoln; Alhasani, Reem Hasaballah; Wong, Aileen; Tchivelekete, Gabriel Mbuta; Zhou, Xiaohu; Patterson, Steven; Bartholomew, Chris; Shu, Xinhua

doi:10.1016/j.bbalip.2021.158927

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…197 Moreover, Borthwick and coworkers 198 showed that STARD3 in ARPE-19 cells can enhance cholesterol efflux, which is located on the membrane of the late endosome and transfers cholesterol from the late endosome to the ER and mitochondria. 199 Almarhoun et al 200 found that the overexpression of STARD3 in ARPE-19 cells can enhance cholesterol efflux in RPE cells by upregulating the expression of ABCA1 and reducing the accumulation of ox-LDL, which ultimately inhibits oxidative stress and inflammation induced by ox-LDL. Regarding TSPO, as a mitochondrial protein, it has the same effect as STARD1.…”

Section: Role Of Cholesterol Metabolism Regulationmentioning

confidence: 99%

Cholesterol metabolism: physiological regulation and diseases

Guo,

Chen,

Zhang

et al. 2024

MedComm

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Cholesterol homeostasis is crucial for cellular and systemic function. The disorder of cholesterol metabolism not only accelerates the onset of cardiovascular disease (CVD) but is also the fundamental cause of other ailments. The regulation of cholesterol metabolism in the human is an extremely complex process. Due to the dynamic balance between cholesterol synthesis, intake, efflux and storage, cholesterol metabolism generally remains secure. Disruption of any of these links is likely to have adverse effects on the body. At present, increasing evidence suggests that abnormal cholesterol metabolism is closely related to various systemic diseases. However, the exact mechanism by which cholesterol metabolism contributes to disease pathogenesis remains unclear, and there are still unknown factors. In this review, we outline the metabolic process of cholesterol in the human body, especially reverse cholesterol transport (RCT). Then, we discuss separately the impact of abnormal cholesterol metabolism on common diseases and potential therapeutic targets for each disease, including CVD, tumors, neurological diseases, and immune system diseases. At the end of this review, we focus on the effect of cholesterol metabolism on eye diseases. In short, we hope to provide more new ideas for the pathogenesis and treatment of diseases from the perspective of cholesterol.

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Section: Role Of Cholesterol Metabolism Regulationmentioning

confidence: 99%

Cholesterol metabolism: physiological regulation and diseases

Guo,

Chen,

Zhang

et al. 2024

MedComm

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“…Considering the evidence that in hepatocytes, the overexpression of STARD3 facilitates the lipidation of exogenous apoA-I and promotes de novo biosynthetic pathways for neutral lipids, leading to an increase in triacylglycerol accumulation ( Soffientini et al, 2014a ) and that overexpression of STARD3 resulted in enhanced cholesterol efflux and reduced intracellular oxidized LDL accumulation ( Almarhoun et al, 2021 ), it can be inferred that STARD3 plays a dual role in lipid metabolism depending on the cell type and this dual role could be determined by the binding to its ligands.…”

Section: The Lutein-binding Protein Stard3mentioning

confidence: 99%

Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions

Balboa,

Saud,

Parra-Ruiz

et al. 2024

Front. Pharmacol.

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The global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasing, now affecting 25%–30% of the population worldwide. MASLD, characterized by hepatic steatosis, results from an imbalance in lipid metabolism, leading to oxidative stress, lipoperoxidation, and inflammation. The activation of autophagy, particularly lipophagy, alleviates hepatic steatosis by regulating intracellular lipid levels. Lutein, a carotenoid with antioxidant and anti-inflammatory properties, protects against liver damage, and individuals who consume high amounts of lutein have a lower risk of developing MASLD. Evidence suggests that lutein could modulate autophagy-related signaling pathways, such as the transcription factor EB (TFEB). TFEB plays a crucial role in regulating lipid homeostasis by linking autophagy to energy metabolism at the transcriptional level, making TFEB a potential target against MASLD. STARD3, a transmembrane protein that binds and transports cholesterol and sphingosine from lysosomes to the endoplasmic reticulum and mitochondria, has been shown to transport and bind lutein with high affinity. This protein may play a crucial role in the uptake and transport of lutein in the liver, contributing to the decrease in hepatic steatosis and the regulation of oxidative stress and inflammation. This review summarizes current knowledge on the role of lutein in lipophagy, the pathways it is involved in, its relationship with STARD3, and its potential as a pharmacological strategy to treat hepatic steatosis.

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“…A recent study revealed that STARD3 may be a target for age-related macular degeneration as it enhances the elimination of intracellular cholesterol and slows the course of the disease [10]. StARrelated lipid transfer protein-3, like other STAR family members, may mediate cholesterol trafficking between late endosomes and other organelles such the endoplasmic reticulum or plasma membrane [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

The significance of StAR-related lipid transfer protein-3 expression in breast cancer

Fararjeh

Kaddumi

Khader

et al. 2022

pjp

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StAR-related lipid transfer domain containing proteins (STARD3) are a group of proteins that contain a steroidogenic acute regulatory protein-related lipid transfer domain. Breast cancer (BC) has been linked to the STARD3 gene. In this study, we sought to confirm the relationship of STARD3 protein expression with clinicopathological characteristics and BC molecular subtypes. Using tissue microarray, we examined the STARD3 protein expression in 200 BC tissues and 20 normal breast tissues. Higher protein expression of STARD3 was found in tumor tissues than normal tissues. One hundred and fifty-two (69.1%) of the 200 cases tested positive for STARD3 (high H-score), while seventy (30.9%) had a low STARD3 H-score. When STARD3 is present, its expression ranges from mild to strong. STARD3 H-score was strongly linked to human epidermal growth factor receptor 2 (HER2)-positive (p < 0.001) and estrogen receptor (ER)-positive (p < 0.009) patients, but not to triple-negative BC patients. STARD3 high H-score was associated with histological grade and tumor size. No significant associations were found with stage of the disease, pathological stage or node status. Our research revealed that STARD3 levels were higher in tissues from malignant BC, and it was associated with HER2 and ER, suggesting that it might be utilized as a marker for BC.

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Overexpression of STARD3 attenuates oxidized LDL-induced oxidative stress and inflammation in retinal pigment epithelial cells

Cited by 5 publications

References 43 publications

Cholesterol metabolism: physiological regulation and diseases

Cholesterol metabolism: physiological regulation and diseases

Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions

The significance of StAR-related lipid transfer protein-3 expression in breast cancer

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