Russell DeBose-Boyd (UTSW) 1: Feedback Regulation of HMG CoA Reductase
นอกจากการดูบทความนี้แล้ว คุณยังสามารถดูข้อมูลที่เป็นประโยชน์อื่นๆ อีกมากมายที่เราให้ไว้ที่นี่: ดูเพิ่มเติม
Dr. Russell DeBoseBoyd describes cellular regulation of cholesterol synthesis, with a focus on endoplasmic reticulumassociated degradation (ERAD) of HMG CoA reductase.
Regulation of cholesterol synthesis is very important: cholesterol is a component of cell membranes and a precursor of steroid hormones and bile acids, yet high levels of cholesterol can be toxic to cells and can contribute to heart disease. Cells in our body obtain cholesterol one of two ways by taking it up from the bloodstream (via lowdensity lipoprotein or LDL) or by synthesizing it intracellularly. In Part 1 of his iBioSeminar, Dr. Russell DeBoseBoyd provides an overview of cholesterol regulation with a focus on HMG CoA reductase, the ratelimiting enzyme of cholesterol synthesis. He describes how the effects of statins, drugs prescribed to lower LDL in the blood, are blunted due to the disruption of feedback control of HMG CoA reductase. In the presence of sterols, HMG CoA reductase protein stability is decreased. This sterolaccelerated degradation of HMG CoA reductase is dependent on the enzyme’s membrane domain in a process known as ERassociated degradation (ERAD). DeBoseBoyd describes his lab’s contributions to a model of HMG CoA reductase ERAD in which polyubiquitination of the enzyme in response to sterols is mediated by two proteins, Insig1 and Insig2, leading to its ERAD by the 26S proteasome.
In Part 2 of his talk, DeBoseBoyd introduces a rare genetic disorder known as Schnyder Corneal Dystrophy (SCD). SCD is characterized by accumulation of cholesterol in the corneas of affected individuals, indicating that the genetic defect in SCD may affect cholesterol synthesis. Mutations in the UBIAD1 gene cause SCD therefore, DeBoseBoyd’s lab sought to understand the role of UBIAD1 in regulation of cholesterol metabolism. UBIAD1 mediates synthesis of Vitamin K2, which requires precursors from the cholesterol synthesis pathway. DeBoseBoyd shares evidence from his lab that UBIAD1 acts as a sensor for levels of the metabolite GGpp, which enhances sterolmediated ERAD of HMG CoA reductase. In the absence of GGpp, UBIAD1 interacts with HMG CoA reductase in the ER membrane and blocks ERAD. In the presence of GGpp, however, UBIAD1 releases HMG CoA reductase, leading to its proteasomal degradation. DeBoseBoyd’s lab also discovered a fascinating spatial regulation of UBIAD1, whereby binding of UBIAD1 to GGpp causes UBIAD1 to accumulate in the Golgi apparatus and away from HMG CoA reductase in the ER. In the second half of his Part 2 lecture, DeBoseBoyd describes analyses of the SCDassociated mutation N102S in UBIAD1. The N102S mutation inhibits the interaction between UBIAD1 and GGpp, such that mutant UBIAD1 is unable to translocate from the ER to the Golgi in the presence of high GGpp. DeBoseBoyd’s lab predicted that the subsequent block of HMG CoA reductase ERAD by mutant UBIAD1 leads to the cholesterol overaccumulation observed in SCD patients. To test this hypothesis, they developed mice with a mutation in UBIAD1 that is equivalent to the N102S mutation observed in SCD patients. They found that, as predicted, mice with mutant UBIAD1 exhibited high levels of HMG CoA reductase protein in their tissues. Finally, they observed that the mutant mice developed corneal opacification, further suggesting that ERAD of HMG CoA reductase is blocked due to the UBIAD1 mutation.
Dr. DeBoseBoyd began undergraduate studies at Southeastern Oklahoma State University where he obtained a BS in Chemistry with minors in Mathematics and Biology in 1993.
Upon completion of undergraduate studies, he was accepted into the Department of Biochemistry and Molecular Biology at the University of Oklahoma Health Sciences Center, and joined the laboratory of Richard D. Cummings, Ph. D. In 1998, he successfully defended his thesis entitled, \”Identification, characterization, and molecular cloning of alpha 1,3 fucosyltransferases in parasitic and nonparasitic helminths.\”
Following his defense, Dr. DeBoseBoyd joined the laboratory of Joseph L. Goldstein, M.D. and Michael S. Brown, M.D. at UT Southwestern Medical Center. After a successful postdoctoral fellowship, Drs. Goldstein and Brown invited Dr. DeBoseBoyd to join the faculty of the Molecular Genetics department as an Assistant Professor in 2003. He became an Established Investigator of the American Heart Association in 2005 and a W.M. Keck Distinguished Young Scholar in Medical Research in 2006. Dr. DeBoseBoyd was promoted to Associate Professor in 2007 and in 2009 he was appointed a Howard Hughes Medical Institute Early Career Scientist. In 2013, Dr. DeBoseBoyd was promoted to Professor and was named the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science in 2016.
Hướng dẫn sử dụng bút tiêm Insulin điều trị tiểu đường
Trong video, Dược sĩ tại nhà thuốc bệnh viện Đa khoa Quốc tế Vinmec sẽ hướng dẫn quý khách hàng cách sử dụng bút Insulin. Bút tiêm insulin là một phát minh quan trọng trong điều trị tiểu đường và ngày càng được nhiều người bệnh sử dụng bởi sự thuận tiện và dễ thực hiện hơn so với phương pháp tiêm thông thường. Tuy nhiên, không ít người bệnh vẫn chưa biết cách sử dụng bút tiêm insulin đúng.
Bước 1: Kiểm tra nhãn bút insulin
Bước 2: Đồng nhất thuốc
Bước 3: Gắn kim tiêm vào bút tiêm
Bước 4: Đuổi khí
Bước 5: Chọn liều
Bước 6: Tiêm thuốc
Bước 7: Tháo kim tiêm
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3 năm Mẹ uống – Mỡ máu cao , Cholesterol – Chia sẻ cho Mọi Người
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HDL \u0026 Reverse Cholesterol Transport [HD]
Updated Comments: August 2017 publication in EHJ shows very high HDL predicts an increased mortality risk (see more details below…)
As shown in older studies (AIMHIGH \u0026 HPS2THRIVE), HDLC increase alone cannot be associated to cardiovascular benefits, especially when LDLC is very low. HDLC remains a marker to assess cardiovascular risk but not a Risk Factor: meaning that raising HDLC is not proven to provide benefit.
A recent data analysis published on August 2017 in the European Heart Journal by Madsen et al. (Eur Heart J 2017;38:2478–2486) referring to the Copenhagen City Heart Study and the Copenhagen General Population Study has shown that the presence of an extremely high concentration of HDL cholesterol is predictive of an increase in allcause mortality in both men and women. This analysis included 52.268 men and 64.240 women and shows a Ushaped relationship between HDL cholesterol concentration and mortality, with an increased risk observed at both low levels and very high levels of HDL cholesterol. The lowest mortality was observed with HDL cholesterol levels of 73.5mg/dL (1.9 mmol/L) in men and 92.8mg/dL (2.4 mmol/L) in women.
Complexity of HDLC functions does not allow simplifications such as to determine CV Benefit just from HDLC concentration (eg: mg/dL) modifications. Number and size of HDLC particles, concentration of ApoA1, and the actual Reverse Cholesterol Efflux need to be considered. More trials are underway to finally conclude on this matter.
LDLC remains the primary treatment target (recent guidelines also mention nonHDL and ApoB as secondary targets).
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HMG CoA Reductase Inhibitors (Statins) | MedMaster | Pharmacology for Nursing Students
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