The 18 kDa Translocator Protein as a Potential Participant in Atherosclerosis

Dimitrova-Shumkovska, Jasmina; Veenman, Leo; Gavish, Moshe

doi:10.5772/25781

“…In parallel, the explained hepatoprotective features of fucoidan also go in favor of this hypothesis considering the impacts of impaired hepatic functioning on lipid homeostasis, regulation of metabolic pathways and lipoprotein uptake [123]. The revealed contribution of ROS in the development of atherosclerotic plaques, as confirmed by increased lipid peroxidation, glutathione depletion, and plasma and tissue protein carbonylation levels, also endorsed investigations of fucoidan as suitable therapeutic for this disease [124][125][126]. A study by Park et al reported the significant decreases in plasma lipid profiles in fucoidan-treated mice with chemically-induced hyperlipidemia, which were comparable with statin effects [127].…”

Section: Liver Injury Cholesterol Atherosclerosis and Fucoidanmentioning

confidence: 94%

Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins

Dimitrova-Shumkovska

¹

,

Krstanoski

²

,

Veenman

³

2020

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Increased interest in natural antioxidants has brought to light the fucoidans (sulfated polysaccharides present in brown marine algae) as highly valued nutrients as well as effective and safe therapeutics against several diseases. Based on their satisfactory in vitro antioxidant potency, researchers have identified this molecule as an efficient remedy for neuropathological as well as metabolic disorders. Some of this therapeutic activity is accomplished by upregulation of cytoprotective molecular pathways capable of restoring the enzymatic antioxidant activity and normal mitochondrial functions. Sirtuin-3 has been discovered as a key player for achieving the neuroprotective role of fucoidan by managing these pathways, whose ultimate goal is retrieving the entirety of the antioxidant response and preventing apoptosis of neurons, thereby averting neurodegeneration and brain injuries. Another pathway whereby fucoidan exerts neuroprotective capabilities is by interactions with P-selectin on endothelial cells, thereby preventing macrophages from entering the brain proper. Furthermore, beneficial influences of fucoidan have been established in hepatocytes after xenobiotic induced liver injury by decreasing transaminase leakage and autophagy as well as obtaining optimal levels of intracellular fiber, which ultimately prevents fibrosis. The hepatoprotective role of this marine polysaccharide also includes a sirtuin, namely sirtuin-1 overexpression, which alleviates obesity and insulin resistance through suppression of hyperglycemia, reducing inflammation and stimulation of enzymatic antioxidant response. While fucoidan is very effective in animal models for brain injury and neuronal degeneration, in general, it is accepted that fucoidan shows somewhat limited potency in liver. Thus far, it has been used in large doses for treatment of acute liver injuries. Thus, it appears that further optimization of fucoidan derivatives may establish enhanced versatility for treatments of various disorders, in addition to brain injury and disease.

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“…It was shown previously that the 18 kDa translocator protein (TSPO) is present throughout the cardiovascular system and may be involved in cardiovascular disorders such as ischemia [36]. At cellular levels, TSPO is present in virtually all of the cells of the cardiovascular system, where they appear to take part in the responses to various challenges that an organism and its cardiovascular system face, including atherosclerosis and accompanying symptoms [22,[39][40][41][42].…”

Section: Potential Functional Commonalities Between Apolipoprotein E mentioning

confidence: 99%

Thrombosis, Atherosclerosis and Atherothrombosis - New Insights and Experimental Protocols

Mijovski¹

2015

1

0

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Previous studies have shown that TSPO as well as apolipoprotein E "po E can be associated with processes such as cholesterol metabolism, oxidative stress, apoptosis, glial activation, inflammation, and immune responses. "s a ligand for cell-surface lipoprotein receptors, apolipoprotein E can prevent atherosclerosis by clearing cholesterol-rich lipoproteins from plasma. Furthermore, TSPO takes part in the regulation of gene expression for proteins involved in adhesion, which potentially may play a role in platelet aggregation. There are indications that the "po E protein is involve in platelet aggregation, while TSPO platelet levels have been found to be increased with various neurological disorders, in particular, in stress-related disorders. The role of platelets in atherogenesis and the potential therapeutic impact of TSPO ligands on disease prevention are of great interest. To determine TSPO binding characteristics in this paradigm, we applied binding assays with [ H]PK on isolated platelets and erythrocyte membranes. The in vivo findings in "po E knockout mice revealed that TSPO levels appear to be enhanced in platelets and erythrocytes of "po E knockout mice, and thus suggest that TSPO and "po E expression may be interconnected in relation to some aspect of the host defense response. Other organs tested, such as liver, testis, brain, heart, aorta, lung, kidney and spleen, did not show a difference in TSPO binding levels between "po E knockout mice and wild-type mice. This suggests that TSPO levels may be part of a feedback control system for steroid production responding to alterations in steroid levels , rather than being regulated by a feed-forward signal provided by cholesterol i.e. TSPO levels in relation to steroidogenesis are not being regulated by cholesterol levels in vivo .

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Thrombosis, Atherosclerosis and Atherothrombosis – New Insights and Experimental Protocols

Dimitrova-Shumkovska¹,

Veenman²,

Roim³

et al. 2015

Thrombosis, Atherosclerosis and Atherothrombosis - New Insights and Experimental Protocols

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Previous studies have shown that TSPO as well as apolipoprotein E "po E can be associated with processes such as cholesterol metabolism, oxidative stress, apoptosis, glial activation, inflammation, and immune responses. "s a ligand for cell-surface lipoprotein receptors, apolipoprotein E can prevent atherosclerosis by clearing cholesterol-rich lipoproteins from plasma. Furthermore, TSPO takes part in the regulation of gene expression for proteins involved in adhesion, which potentially may play a role in platelet aggregation. There are indications that the "po E protein is involve in platelet aggregation, while TSPO platelet levels have been found to be increased with various neurological disorders, in particular, in stress-related disorders. The role of platelets in atherogenesis and the potential therapeutic impact of TSPO ligands on disease prevention are of great interest. To determine TSPO binding characteristics in this paradigm, we applied binding assays with [ H]PK on isolated platelets and erythrocyte membranes. The in vivo findings in "po E knockout mice revealed that TSPO levels appear to be enhanced in platelets and erythrocytes of "po E knockout mice, and thus suggest that TSPO and "po E expression may be interconnected in relation to some aspect of the host defense response. Other organs tested, such as liver, testis, brain, heart, aorta, lung, kidney and spleen, did not show a difference in TSPO binding levels between "po E knockout mice and wild-type mice. This suggests that TSPO levels may be part of a feedback control system for steroid production responding to alterations in steroid levels , rather than being regulated by a feed-forward signal provided by cholesterol i.e. TSPO levels in relation to steroidogenesis are not being regulated by cholesterol levels in vivo .

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The 18 kDa Translocator Protein as a Potential Participant in Atherosclerosis

Cited by 3 publications

References 110 publications

Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins

Potential Beneficial Actions of Fucoidan in Brain and Liver Injury, Disease, and Intoxication—Potential Implication of Sirtuins

Thrombosis, Atherosclerosis and Atherothrombosis - New Insights and Experimental Protocols

Thrombosis, Atherosclerosis and Atherothrombosis – New Insights and Experimental Protocols

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