scholarly journals Modulation of intrahepatic cholesterol trafficking: evidence by in vivo antisense treatment for the involvement of sterol carrier protein-2 in newly synthesized cholesterol transport into rat bile

1996 ◽  
Vol 317 (3) ◽  
pp. 681-687 ◽  
Author(s):  
Luigi PUGLIELLI ◽  
Attilio RIGOTTI ◽  
Ludwig AMIGO ◽  
Liliana NUÑEZ ◽  
Aldo V. GRECO ◽  
...  

Biliary cholesterol represents one of the two major excretory pathways for sterol elimination from the body and plays a central role in cholesterol gallstone formation. Biliary cholesterol originates from a precursor pool of preformed and newly synthesized free cholesterol. Although it has been suggested that newly synthesized and preformed biliary cholesterol are secreted by independent pathways, the specific cellular and molecular mechanisms are unknown. We used male Wistar rats to study the time-course of the appearance of newly synthesized cholesterol, phosphatidylcholine and protein into bile. The specific role of sterol carrier protein-2 (SCP-2) in the transport of newly synthesized biliary cholesterol was evaluated by an in vivo antisense oligonucleotide approach. In contrast to [14C]phosphatidylcholine and [35S]proteins, the time-course of [14C]cholesterol appearance into bile was rapid, and microtubule- and Golgi-independent. In vivo SCP-2 antisense treatment reduced and delayed the appearance of biliary [14C]cholesterol. Furthermore, hepatic SCP-2 expression increased more than 3-fold over control values in rats that had been treated with diosgenin to increase biliary secretion of newly synthesized cholesterol. These results suggest that SCP-2 is necessary for the rapid transport of newly synthesized cholesterol into bile and that hepatocytes can induce SCP-2 expression according to the rate of biliary secretion of newly synthesized cholesterol.

1998 ◽  
Vol 336 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Michael FUCHS ◽  
Frank LAMMERT ◽  
David Q.-H. WANG ◽  
Beverly PAIGEN ◽  
Martin C. CAREY ◽  
...  

In inbred mice, susceptibility to cholesterol gallstone disease is conferred by Lith genes, which in part promote hypersecretion of cholesterol into bile in response to a high-fat/cholesterol/cholic acid (lithogenic) diet. Because cytosolic sterol carrier protein 2 (SCP2) is believed to participate in cellular cholesterol trafficking and is elevated in the liver cytosol of cholesterol gallstone patients, we defined the hepatic expression of SCP2 during cholesterol gallstone formation in gallstone-susceptible C57L and gallstone-resistant AKR mice fed the lithogenic diet. Steady-state cytosolic SCP2 levels in C57L, but not AKR mice increased as a function of time and were correlated positively with biliary cholesterol hypersecretion, cholesterol saturation indices of gall-bladder biles and the appearance of liquid and solid cholesterol crystals leading to gallstone formation. Steady-state mRNA levels increased co-ordinately, consistent with regulation of SCP2 expression at the transcriptional level. Our results suggest that overexpression of SCP2 contributes to biliary cholesterol hypersecretion and the pathogenesis of gallstones in genetically susceptible mice. Because of the different chromosomal localizations of the Lith and Scp2 genes, we postulate that Lith genes control SCP2 expression indirectly.


Author(s):  
Hirunika Perera ◽  
Tharaka Wijerathna

Cholesterol is one of the most vital compounds for animals as it is involved in various biological processes and acts as the structural material in the body. However, insects do not have some of the essential enzymes in the cholesterol biosynthesis pathway and this makes them dependent on dietary cholesterol. Thus, the blocking of cholesterol uptake may have detrimental effects on the survival of the insect. Utilizing this character, certain phytochemicals can be used to inhibit mosquito sterol carrier protein-2 (AeSCP-2) activity via competitive binding and proven to have effective insecticidal activities against disease-transmitting mosquitoes and other insect vectors. A range of synthetic compounds, phytochemicals, and synthetic analogs of phytochemicals are found to have AeSCP-2 inhibitory activity. Phytochemicals such as alpha-mangostin can be considered as the most promising group of compounds when considering the minimum environmental impact and availability at a low cost. Once the few limitations such as very low persistence in the environment are addressed successfully, these chemicals may be used as an effective tool for controlling mosquitoes and other disease-transmitting vector populations.


PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e18030 ◽  
Author(s):  
Rong Peng ◽  
Vilena I. Maklokova ◽  
Jayadevi H. Chandrashekhar ◽  
Que Lan

Biochemistry ◽  
2004 ◽  
Vol 43 (23) ◽  
pp. 7288-7306 ◽  
Author(s):  
Minglong Zhou ◽  
Rebecca D. Parr ◽  
Anca D. Petrescu ◽  
H. Ross Payne ◽  
Barbara P. Atshaves ◽  
...  

Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.


2010 ◽  
Vol 47 (2) ◽  
pp. 249-257 ◽  
Author(s):  
Ryan T. Larson ◽  
Jeffrey M. Lorch ◽  
Julia W. Pridgeon ◽  
James J. Becnel ◽  
Gary G. Clark ◽  
...  

2000 ◽  
Vol 119 (6) ◽  
pp. 1708-1719 ◽  
Author(s):  
Silvana Zanlungo ◽  
Ludwig Amigo ◽  
Hegaly Mendoza ◽  
Juan Francisco Miquel ◽  
Carlos Vío ◽  
...  

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