Lipid droplet proteins and metabolic diseases

Lipid droplets (LDs) are ubiquitous cellular organelles for lipid storage which are composed of a neutral lipid core bounded by a protein decorated phospholipid monolayer. Although lipid storage is their most obvious function, LDs are far from inert as they participate in maintaining lipid homeostasis through lipid synthesis, metabolism, and transportation. Furthermore, they are involved in cell signaling and other molecular events closely associated with human disease such as dyslipidemia, obesity, lipodystrophy, diabetes, fatty liver, atherosclerosis, and others. The last decade has seen a great increase in the attention paid to LD biology. Regardless, many fundamental features of LD biology remain obscure. In this review, we will discuss key aspects of LD biology including their biogenesis, growth and regression. We will also summarize the current knowledge about the role LDs play in human disease, especially from the perspective of the dynamics of the associated proteins. This article is part of a Special issue entitled Cardiac adaptations to obesity, diabetes and insulin resistance, edited by Professors Jan F.C. Glatz, Jason R.B. Dyck and Christine Des Rosiers.     

5—羟色胺对肺动脉平滑肌细胞在缺氧条件下增殖的作用

本研究应用细胞培养、＾３Ｈ－ＴｄＲ掺入,核酸分子杂交、免疫组织化学染色技术,探讨无氧（０％Ｏ２＋９５％Ｎ２＋５％ＣＯ２）和／或低氧（２．５￣３％Ｏ２＋９２％Ｎ２＋５％ＣＯ２）对新生小牛肺动脉平滑肌细胞增殖和５－羟色胺转载体基因表达的影响。结果表明：无氧２４ｈ可刺激ＰＡＳＭ的ＤＮＡ合成,＾３Ｈ－ＴｄＲ的掺入增加（Ｐ〈０．０５）,加入５－羟色胺能非常显著地促进无氧ＰＡＳＭ增殖（Ｐ〈０．００１）,而对常     

缺氧对体外培养的肺动脉平滑肌细胞形态及增殖的影响

本实验应用形态学、免疫组化染色,＾３Ｈ－ＴｄＲ掺入、流式细胞等技术探讨缺氧（〈１％Ｏ２和２．５％Ｏ２）对肺动脉平滑肌细胞（ＰＡＳＭ）形态及增殖的影响。结果表明：缺氧２４ｈ使ＰＡＳＭ表型从收缩型向合成型转换,胞浆内ＳＭ－ａ ａｃｔｉｎ减少,线粒体和粗面内质网增多,缺氧４８ｈ以后线粒体肿胀,空泡化,内质网扩张,胞浆内出现髓鞘样结构。流式细胞分析显示缺氧ＰＡＳＭ Ｇ２／Ｍ期细胞比例明显增多（Ｐ〈０．００     

内皮素对麻醉大鼠动脉压力感受器反射的调制作用

在27只隔离灌流颈动脉窦区的麻醉大鼠,观察了内皮素（ET-1）对动脉压力感受器反射的调制作用。结果如下：（1）在颈动脉窦区灌流1nmol／L的ET-1时,压力感受器机能曲线向左下方移位,曲线的最大斜率（PS）由0.40±0.02增至0.51±0.02kPa／kPa（P＜0.01）,压力感受器反射性血压下降幅度（RD）由5.66±0.23增至6.76±0.22kPa（P＜0.01）。由此提示,这一剂量的FT-1对压力感受器反射有易化作用。（2）用10nmol／L的ET-1灌流时,压力感受器机能曲线则向右上方移位,PS降至0.28±0.01kPa／kPa（P＜0.01）,RD降至4．16±0.19kPa（P＜0.01）;100nmol／L的ET-1可使压力感受器机能曲线向右上方移位更为明显,PS降至0.19±0.03kPa（P＜0.001）,RD进一步降至3.33±0.38kPa（P＜0.001）。这些结果表明,上述两种剂量的ET-1对压力感受器反射有抑制作用。（3）ETA受体选择性阻断剂BQ123（0.15μmol／L）可以阻断ET-1（10nmol／L）对压力感受器反射的抑制效应。（4）预先灌流KATP通道阻断剂格列苯脲（10μmol／L）,也可阻断ET-1的效应。综上所述,ET-1对压力感受器反射有双重效应,低剂量时有易化作用,而较高剂量时则有抑制作用,后一作用由ET-1型受体介导并有KATP通道的参与。     

Characterization of a caveolin‐1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy

Congenital generalized lipodystrophy (CGL) and pulmonary arterial hypertension (PAH) have recently been associated with mutations in the caveolin‐1 ( CAV1 ) gene, which encodes the primary structural protein of caveolae. However, little is currently known about how these CAV1 mutations impact caveolae formation or contribute to the development of disease. Here, we identify a heterozygous F160X CAV1 mutation predicted to generate a C‐terminally truncated mutant protein in a patient with both PAH and CGL using whole exome sequencing, and characterize the properties of CAV1 , caveolae‐associated proteins and caveolae in skin fibroblasts isolated from the patient. We show that morphologically defined caveolae are present in patient fibroblasts and that they function in mechanoprotection. However, they exhibited several notable defects, including enhanced accessibility of the C‐terminus of wild‐type CAV1 in caveolae, reduced colocalization of cavin‐1 with CAV1 and decreased stability of both 8S and 70S oligomeric CAV1 complexes that are necessary for caveolae formation. These results were verified independently in reconstituted CAV1 ^?/? mouse embryonic fibroblasts. These findings identify defects in caveolae that may serve as contributing factors to the development of PAH and CGL and broaden our knowledge of CAV1 mutations associated with human disease.      

Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease

Muscle mitochondrial content is tightly regulated, and requires the expression of both nuclear and mitochondrial genes. In addition, muscle mitochondrial content is a major determinant of aerobic exercise capacity in healthy subjects. The current study was designed to test the hypothesis that in healthy humans, muscle mitochondrial DNA (mtDNA) content is correlated with citrate synthase activity (a representative nuclear-encoded mitochondrial enzyme) and aerobic exercise capacity as defined by whole-body peak oxygen consumption (VO2). Furthermore, it was postulated that these relationships might be altered with disease. Twelve healthy and five paraplegic subjects underwent exercise testing and vastus lateralis muscle biopsy sampling. An additional ten healthy subjects and eight patients with unilateral peripheral arterial disease (PAD) underwent exercise testing and gastrocnemius muscle biopsy sampling. Citrate synthase activity and mtDNA content were positively correlated in the vastus lateralis muscles from the healthy subjects. This relationship was similar in muscle from paraplegic subjects. mtDNA content was positively correlated with peak VO2 in the healthy subjects and in the paraplegic subjects in whom peak VO2 had been elicited by functional electrical stimulation of the muscle. In contrast, the PAD subjects demonstrated higher mtDNA contents than would have been predicted based on their claudication-limited peak VO2. Thus, in healthy humans there are strong relationships between muscle mtDNA content and both muscle citrate synthase activity and peak VO2. These relationships are consistent with coordinant nuclear DNA and mtDNA expression, and with mitochondrial content being a determinant of aerobic exercise capacity. The relationships seen in healthy humans are quantitatively similar in paraplegic patients, but not in patients with PAD, a disease which is associated with a metabolic myopathy. The relationships between mtDNA content, mitochondrial enzyme activities and exercise capacity provide insight into the physiologic and pathophysiologic regulation of muscle mitochondrial expression.     

木本植物木质部空穴和栓塞化研究(综述)

木本植物木质部空穴和栓塞化现象的发现至今已近80年历史,国外学者对此做了较多的研究,国内此方面的研究极少。木质部空穴和栓塞化研究是木本植物体内水分传输研究的前沿所在,不同学者在不同地区对不同材料的研究结果各异,争议颇多。本文对这一研究方向近年来的资料作了概括和总结,包括栓塞化现象的发现、检测方法、诱因及形成机理、木质部栓塞化同输水结构间的关系等方面。     

Cellular mechanosignaling in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a vasculopathy characterized by sustained elevated pulmonary arterial pressures in which the pulmonary vasculature undergoes significant structural and functional remodeling. To better understand disease mechanisms, in this review article we highlight recent insights into the regulation of pulmonary arterial cells by mechanical cues associated with PAH. Specifically, the mechanobiology of pulmonary arterial endothelial cells (PAECs), smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs) has been investigated in vivo, in vitro, and in silico. Increased pulmonary arterial pressure increases vessel wall stress and strain and endothelial fluid shear stress. These mechanical cues promote vasoconstriction and fibrosis that contribute further to hypertension and alter the mechanical milieu and regulation of pulmonary arterial cells.     

Physicochemical properties of arterial elastin and its associated glycoproteins

Microfibrillar glycoproteins are a significant component of vascular elastic tissue, but little is known about their contribution to vascular physiology and pathology. We have investigated some physicochemical properties of the glycoproteins that may be pertinent to these roles. Because of the difficulty in isolating intact glycoproteins in a form and quantity suitable for physicochemical examination, we based our analysis on a comparison of the properties of porcine thoracic aorta and pulmonary artery extracted with GuHCl and collagenase (preparation GC) and after further treatment with dithioerythritol to remove glycoproteins (preparation GC/DTE). Amino acid analysis showed that GC/DTE had the amino acid composition of pure elastin while GC contained a higher proportion of polar amino acids, particularly in the aortic preparation. GC stained with alcian blue, particularly in the intimal region, but GC/DTE did not. GC had a higher water content and a slower viscoelastic response and the circumferential elastic modulus was approximately 50% lower (whether expressed in terms of sample weight or elastin content). Clearly, therefore, the microfibrils do not stiffen the network and may prevent the alignment of elastin fibers in the circumferential direction. Their effect on hydration may arise either because they impose mechanical constraints on the geometry of the network or because they modify the inter‐ and intramolecular hydrophobic or electrostatic interactions that influence the tissue organization and hydration. Molecular probe measurements of the intrafibrillar pore structure using radiolabeled and fluorescent probes showed that removal of the microfibrils caused a slight decrease in the extrafibrillar water space and a larger decrease in the intrafibrillar water space. Sucrose, a small probe molecule, was able to penetrate most of the intrafibrillar water space when microfibrils were present but was virtually excluded when they were not. Potentiometric titration and radiotracer assays of ion binding both showed that the microfibrils contribute a considerable negative charge (−9 μmoles/g wet tissue in the aortic preparation and −16 μmoles/g wet weight in the pulmonary artery) and increase calcium binding by approximately 30%. © 1999 John Wiley & Sons, Inc. Biopoly 49: 255–265, 1999     

血清VEGF，IGF-1和CA125水平与子宫动脉栓塞术(UAE)治疗子宫腺肌症的相关性

目的:探讨血清血管内皮生长因子(VEGF)、胰岛素样生长因子-1(IGF-1)和CA125水平和子宫动脉栓塞术(UAE)治疗子宫腺肌症的之间的相关性。方法:选择接受子宫动脉栓塞术治疗的39例子宫腺肌症患者作为患者组,取同时期参加健康体检的30名健康者作为健康对照组。用ELISA法检测子宫腺肌症患者子宫动脉栓塞术前和术后不同时点血清VEGF、IGF-1、CA125的水平,评估子宫动脉栓塞术后的患者的疗效。结果:34例痛经患者术后1个月开始改善,最终29例完全缓解,有效率85.2%。患者组治疗前血清VEGF、IGF-1、CA125水平均显著高于健康对照组(P0.05)。子宫动脉栓塞术治疗后,患者组血清IGF-1、VEGF和CA125的水平与治疗前相比均显著降低,术后6月,恢复正常水平。结论:血清IGF-1、VEGF、CA125的变化可能在子宫动脉栓塞术治疗子宫腺肌症中作为疗效和预后评估指标。