Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation
Eur J Cell Biol. 2023 Mar 13;102(2):151310. doi: 10.1016/j.ejcb.2023.151310. Online ahead of print.ABSTRACTSilicosis is considered an irreversible chronic inflammatory disease caused by the inhalation of crystalline silica (cSiO2). The cycle of inflammation that drives silicosis and other particle-caused respiratory diseases is mediated by NLRP3 inflammasome activity in macrophages resulting in the release of IL-1β. Lysosomal membrane permeability (LMP) initiated by inhaled particles is the key regulatory step in leading to NLRP3 activity. In addition to its role in LMP, the lysosome is crucial to cellular cholesterol tra...
Source: European Journal of Cell Biology - March 19, 2023 Category: Cytology Authors: Rebekah L Kendall Andrij Holian Source Type: research
N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann-Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - February 21, 2023 Category: Drugs & Pharmacology Authors: Hiroyuki Nakamura Yuan Zhou Yuka Sakamoto Ayako Yamazaki Eon Kurumiya Risa Yamazaki Kyota Hayashi Yoshitoshi Kasuya Kazuaki Watanabe Junya Kasahara Mamoru Takabatake Koichiro Tatsumi Ichiro Yoshino Takuya Honda Toshihiko Murayama Source Type: research
Rab7a-mTORC1 signaling-mediated cholesterol trafficking from the lysosome to mitochondria ameliorates hepatic lipotoxicity induced by aflatoxin B1 exposure
Chemosphere. 2023 Feb 6:138071. doi: 10.1016/j.chemosphere.2023.138071. Online ahead of print.ABSTRACTAflatoxin B1 (AFB1) is a common contaminant in many foodstuffs and is considered a public health concern worldwide due to its hepatotoxicity caused by lipid metabolism disorders. However, the molecular mechanism underlying AFB1-induced lipotoxicity-dependent liver injury via regulating cholesterol metabolism remains unclear. We established a cholesterol trafficking disorder-mediated hepatic lipotoxicity model with AFB1 mixture exposure in vitro (HepaRG and HepG2 cells, 1.6 μM for 36 h) and in vivo (C57BL/6 mice, 3 mg kg-1...
Source: Chemosphere - February 8, 2023 Category: Chemistry Authors: Jin-Xian Lin Chi-Yu Xu Xin-Mou Wu Lin Che Ting-Yu Li Su-Min Mo Dong-Bei Guo Zhong-Ning Lin Yu-Chun Lin Source Type: research
Rab7a-mTORC1 signaling-mediated cholesterol trafficking from the lysosome to mitochondria ameliorates hepatic lipotoxicity induced by aflatoxin B1 exposure
Chemosphere. 2023 Feb 6:138071. doi: 10.1016/j.chemosphere.2023.138071. Online ahead of print.ABSTRACTAflatoxin B1 (AFB1) is a common contaminant in many foodstuffs and is considered a public health concern worldwide due to its hepatotoxicity caused by lipid metabolism disorders. However, the molecular mechanism underlying AFB1-induced lipotoxicity-dependent liver injury via regulating cholesterol metabolism remains unclear. We established a cholesterol trafficking disorder-mediated hepatic lipotoxicity model with AFB1 mixture exposure in vitro (HepaRG and HepG2 cells, 1.6 μM for 36 h) and in vivo (C57BL/6 mice, 3 mg kg-1...
Source: Chemosphere - February 8, 2023 Category: Chemistry Authors: Jin-Xian Lin Chi-Yu Xu Xin-Mou Wu Lin Che Ting-Yu Li Su-Min Mo Dong-Bei Guo Zhong-Ning Lin Yu-Chun Lin Source Type: research
Rab7a-mTORC1 signaling-mediated cholesterol trafficking from the lysosome to mitochondria ameliorates hepatic lipotoxicity induced by aflatoxin B1 exposure
Chemosphere. 2023 Feb 6:138071. doi: 10.1016/j.chemosphere.2023.138071. Online ahead of print.ABSTRACTAflatoxin B1 (AFB1) is a common contaminant in many foodstuffs and is considered a public health concern worldwide due to its hepatotoxicity caused by lipid metabolism disorders. However, the molecular mechanism underlying AFB1-induced lipotoxicity-dependent liver injury via regulating cholesterol metabolism remains unclear. We established a cholesterol trafficking disorder-mediated hepatic lipotoxicity model with AFB1 mixture exposure in vitro (HepaRG and HepG2 cells, 1.6 μM for 36 h) and in vivo (C57BL/6 mice, 3 mg kg-1...
Source: Chemosphere - February 8, 2023 Category: Chemistry Authors: Jin-Xian Lin Chi-Yu Xu Xin-Mou Wu Lin Che Ting-Yu Li Su-Min Mo Dong-Bei Guo Zhong-Ning Lin Yu-Chun Lin Source Type: research
NDUFA4L2 reduces mitochondrial respiration resulting in defective lysosomal trafficking in clear cell renal cell carcinoma
Cancer Biol Ther. 2023 Dec 31;24(1):2170669. doi: 10.1080/15384047.2023.2170669.ABSTRACTIn clear cell renal cell carcinoma (ccRCC), activation of hypoxic signaling induces NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) expression. Over 90% of ccRCCs exhibit overexpression of NDUFA4L2, which we previously showed contributes to ccRCC proliferation and survival. The function of NDUFA4L2 in ccRCC has not been fully elucidated. NDUFA4L2 was reported to reduce mitochondrial respiration via mitochondrial complex I inhibition. We found that NDUFA4L2 expression in human ccRCC cells increases the extracellul...
Source: Cancer Biology and Therapy - February 1, 2023 Category: Cancer & Oncology Authors: Jaclyn M Kubala Kristian B Laursen Ryan Schreiner Ryan M Williams Johannes C van der Mijn Michael J Crowley Nigel P Mongan David M Nanus Daniel A Heller Lorraine J Gudas Source Type: research
SMPD1 gene variants in patients with β-Thalassemia major
CONCLUSION: These results imply that the clinical and laboratory findings and some features of disease progression in patients with β-thalassemia major are similar to those of Niemann-Pick disease. They also suggest that SMPD1 gene c.132_143del, p.A46_L49del (c.108GCTGGC[4] (p.38AL[4])) (rs3838786) variant may underlie these clinical findings in patients with β-thalassemia major.PMID:36725747 | DOI:10.1007/s11033-023-08275-x (Source: Molecular Biology Reports)
Source: Molecular Biology Reports - February 1, 2023 Category: Molecular Biology Authors: Fadime Ersoy Dursun Filiz Özen Source Type: research
NDUFA4L2 reduces mitochondrial respiration resulting in defective lysosomal trafficking in clear cell renal cell carcinoma
Cancer Biol Ther. 2023 Dec 31;24(1):2170669. doi: 10.1080/15384047.2023.2170669.ABSTRACTIn clear cell renal cell carcinoma (ccRCC), activation of hypoxic signaling induces NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) expression. Over 90% of ccRCCs exhibit overexpression of NDUFA4L2, which we previously showed contributes to ccRCC proliferation and survival. The function of NDUFA4L2 in ccRCC has not been fully elucidated. NDUFA4L2 was reported to reduce mitochondrial respiration via mitochondrial complex I inhibition. We found that NDUFA4L2 expression in human ccRCC cells increases the extracellul...
Source: Cancer Biology and Therapy - February 1, 2023 Category: Cancer & Oncology Authors: Jaclyn M Kubala Kristian B Laursen Ryan Schreiner Ryan M Williams Johannes C van der Mijn Michael J Crowley Nigel P Mongan David M Nanus Daniel A Heller Lorraine J Gudas Source Type: research
