Inhibition of CD36 and Nogo-B expression inhibited the proliferation and migration of triple negative breast cancer cells / 生物工程学报

Cluster of differentiation 36 (CD36) is a membrane glycoprotein receptor capable of binding and transporting fatty acid. Nogo-B regulates the metabolism of fatty acids in the liver and affects the development of liver cancer. To date, it remains unclear whether the interaction between CD36 and Nogo-B affects the proliferation and migration of breast cancer cells. In the current study, we aimed to determine whether the interference of CD36 and Nogo-B affects the proliferation and migration of triple-negative breast cancer (TNBC) cells. The results showed that inhibition of CD36 or Nogo-B alone can inhibit the proliferation and migration of TNBC cells, and the inhibitory effect was more pronounced when CD36 and Nogo-B were inhibited simultaneously. Meanwhile, it was found that inhibition of CD36 and Nogo-B expression can inhibit the expression of Vimentin, B-cell lympoma-2 (BCL2) and proliferating cell nuclear antigen (PCNA). In vivo, knockdown of CD36 or Nogo-B in E0771 cells reduced its tumorigenic ability, which was further enhanced by knockdown of CD36 and Nogo-B simultaneously. Mechanistically, inhibition of CD36 and Nogo-B expression can decrease fatty acid binding protein 4 (FABP4) and fatty acid transport protein 4 (FATP4) expression. Moreover, overexpression of CD36 and Nogo-B-induced cell proliferation was attenuated by FABP4 siRNA, indicating that inhibition of CD36 and Nogo-B expression could inhibit the absorption and transport of fatty acids, thereby inhibiting the proliferation and migration of TNBC. Furthermore, inhibition of CD36 and Nogo-B expression activated the P53-P21-Rb signaling pathway which contributed to the CD36 and Nogo-B-inhibited proliferation and migration of TNBC. Taken together, the results suggest that inhibition of CD36 and Nogo-B can reduce the proliferation and migration of TNBC, which provides new targets for the development of drugs against TNBC.

Essential Oil from Alpinia zerumbet Rhizome Inhibits Macrophage-derived Foam Cell Formation Via Modulating Expression of CD36 and ABCA1 / 中国实验方剂学杂志

Objective::To clarify the inhibitory effect of essential oil from Alpinia zerumbet rhizome (EOFAZ) on oxidized low-density lipoprotein (ox-LDL)-induced transformation of macrophage into foam cell and explore its possible mechanism. Method::THP-1 monocyte was incubated with 100 μg·L-1 phorbol myristate acetate (PMA) to grow into macrophage, experiment was divided into 4 groups as follows, control group, model group (80 mg·L-1 ox-LDL), EOFAZ at low dose (80 mg·L-1 ox-LDL+ 4 μg·L-1 EOFAZ)and EOFAZ at high dose (80 g·L-1 ox-LDL+ 20 μg·L-1 EOFAZ). Mathye thiazolye telrazliurn (MTT) method was employed to examine the influence of EOFAZ on macrophage viability. Western blot was used to analyze the expression level of cluster of differentiation 36(CD36) and ATP-binding cassette transporter A1(ABCA1) protein in macrophage. Enzyme-linked immunosorbent assay (ELISA) was used to detect cholesteryl ester contents in macrophage. Oil red O staining was applied to determine the accumulation of lipids in macrophage. Result::EOFAZ showed non-toxic effect on macrophage. Compared to control group, macrophage in model group displayed higher level of cholesteryl ester and lipid droplet(P<0.01), as well as significant increasing of CD36 expression (P<0.01), but no effect on ABCA1 expression. EOFAZ notably reduced the contents of lipids and cholesteryl ester(P<0.01), down-regulated expression of CD36 and up-regulated expression of ABCA1 in macrophage in comparison with the model group(P<0.01), indicating that EOFAZ inhibited transformation of macrophage into foam cell. Conclusion::EOFAZ could inhibit ox-LDL-induced transformation of macrophage into foam cell, the underlying mechanism may involves its ability to increase CD36 expression and decrease ABCA1 expression in macrophage.

CD36 (SR-B2) as a Target to Treat Lipid Overload-Induced Cardiac Dysfunction

The heart faces the challenge of adjusting the rate of fatty acid uptake to match myocardial demand for energy provision at any given moment, avoiding both too low uptake rates, which could elicit an energy deficit, and too high uptake rates, which pose the risk of excess lipid accumulation and lipotoxicity. The transmembrane glycoprotein cluster of differentiation 36 (CD36), a scavenger receptor (B2), serves many functions in lipid metabolism and signaling. In the heart, CD36 is the main sarcolemmal lipid transporter involved in the rate-limiting kinetic step in cardiac lipid utilization. The cellular fatty acid uptake rate is determined by the presence of CD36 at the cell surface, which is regulated by subcellular vesicular recycling from endosomes to the sarcolemma. CD36 has been implicated in dysregulated fatty acid and lipid metabolism in pathophysiological conditions, particularly high-fat diet-induced insulin resistance and diabetic cardiomyopathy. Thus, in conditions of chronic lipid overload, high levels of CD36 are moved to the sarcolemma, setting the heart on a route towards increased lipid uptake, excessive lipid accumulation, insulin resistance, and eventually contractile dysfunction. Insight into the subcellular trafficking machinery of CD36 will provide novel targets to treat the lipid-overloaded heart. A screen for CD36-dedicated trafficking proteins found that vacuolar-type H⁺-ATPase and specific vesicle-associated membrane proteins, among others, were uniquely involved in CD36 recycling. Preliminary data suggest that these proteins may offer clues on how to manipulate myocardial lipid uptake, and thus could be promising targets for metabolic intervention therapy to treat the failing heart.

Vasoprotective effects of rice bran water extract on rats fed with high-fat diet

Objective: To elucidate the protective effects of rice bran water extract on the expression of endothelial nitric oxide synthase (eNOS), nuclear factor-kappa B (NF-kB), and a cluster of differentiation 36 (CD36) in the vasculature of high-fat diet-fed rats. Methods: Male Sprague-Dawley rats were divided into three groups. Group I served as control, Group II was treated with high-fat diet, and Group III was treated with high-fat diet and rice bran water extract at 2 205 mg/kg/day. After four weeks, the metabolic parameters, malondialdehyde as a marker of oxidative stress, and histological features of the aorta were evaluated. The levels of transcripts and proteins in aorta were determined by real-time PCR and Western blot analysis, respectively. Results: In comparison with the Group II, rice bran water extract administration resulted in a significant reduction in body weight, visceral fat tissue weights, blood glucose levels, and serum total-cholesterol and free fatty acid levels in Group III. Serum triglyceride levels tended to decrease in the Group III. Also, rice bran water extract administration obviously decreased malondialdehyde levels in both serum and aorta. Interestingly, rice bran water extract treatment demonstrated a significant up-regulation of eNOS expression and down-regulation of NF-kB p65 and CD36 expressions. Nonetheless, all groups showed normal histology of aorta. Conclusions: Rice bran water extract exhibited vasoprotective effects in the high-fat diet-induced obesity condition by modulating the expression of eNOS, NF-kB, and CD36 and metabolic parameters.

Vasoprotective effects of rice bran water extract on rats fed with high-fat diet

Objective To elucidate the protective effects of rice bran water extract on the expression of endothelial nitric oxide synthase (eNOS), nuclear factor-kappa B (NF-κB), and a cluster of differentiation 36 (CD36) in the vasculature of high-fat diet-fed rats. Methods Male Sprague-Dawley rats were divided into three groups. Group I served as control, Group II was treated with high-fat diet, and Group III was treated with high-fat diet and rice bran water extract at 2 205 mg/kg/day. After four weeks, the metabolic parameters, malondialdehyde as a marker of oxidative stress, and histological features of the aorta were evaluated. The levels of transcripts and proteins in aorta were determined by real-time PCR and Western blot analysis, respectively. Results In comparison with the Group II, rice bran water extract administration resulted in a significant reduction in body weight, visceral fat tissue weights, blood glucose levels, and serum total-cholesterol and free fatty acid levels in Group III. Serum triglyceride levels tended to decrease in the Group III. Also, rice bran water extract administration obviously decreased malondialdehyde levels in both serum and aorta. Interestingly, rice bran water extract treatment demonstrated a significant up-regulation of eNOS expression and down-regulation of NF-κB p65 and CD36 expressions. Nonetheless, all groups showed normal histology of aorta. Conclusions Rice bran water extract exhibited vasoprotective effects in the high-fat diet-induced obesity condition by modulating the expression of eNOS, NF-κB, and CD36 and metabolic parameters.