THE EVOLVING CONCEPT OF CAVEOLINS AND INTERMEDIARY ROLE IN VARIOUS MECHANISMS VIA BIOMOLECULAR PATHWAYS

INDIAN DRUGS ◽  
2018 ◽  
Vol 55 (04) ◽  
pp. 7-17
Author(s):  
P. K. Upadhyay ◽  
◽  
V. K. Vishwakarma
Keyword(s):  
Nitric Oxide ◽  
Fatty Acid ◽  
Membrane Proteins ◽  
Cancer Progression ◽  
Ischemic Preconditioning ◽  
Mammalian Cells ◽  
Cholesterol Homeostasis ◽  
Integral Membrane Proteins ◽  
Acid Uptake ◽  
Cardiovascular Research

Caveolins are integral membrane proteins which consist of caveolae, present in plasma membrane. Many researchers have reported the role of caveolae in major physiological conduits of the mammalian cells, including cholesterol homeostasis, transcytosis and endocytosis. Caveolin also play a role in ischemic preconditioning of heart, postmenopausal women, brain microvessels, cancer progression and Alzheimer’s disease. Attenuation of myocardial protection in diabetic heart may be due to decrease in the ischemic preconditioning mediated release of nitric oxide, upregulation of caveolin and consequently decrease in activity of endothelial nitric oxide synthase (eNOS). Caveolin alogwith integral membrane proteins overexpress in a huge range of tumor entities, while hormonal changes cause variation in caveolin expression. Under ovariectomy conditions, eNOS inhibitory action occurs because of interaction between eNOS and caveolin. Some new concepts explain that multiple proteins, including caveolin-1 alter trans-membrane flux of fatty acid and play role in fatty acid uptake. Caveolin can be useful in the controlling of cardiovascular system (CVS) and brain disease using various predicaments. New intermediate steps have been discovered which correlate various mechanisms of ischemic preconditioning, cardiopotection and eNOS in the field of cardiovascular research.

Dietary fatty acids and CD36-mediated cholesterol homeostasis: potential mechanisms

2020 ◽  
pp. 1-14 ◽  
Author(s):  
Elif Ulug ◽  
Reyhan Nergiz-Unal
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesterol Metabolism ◽  
Fatty Acid Pattern ◽  
Dietary Fatty Acids ◽  
Cholesterol Homeostasis ◽  
Acid Uptake ◽  
Pufa Ratio ◽  
Mortality And Morbidity ◽  
Cd36 Receptor

Abstract Currently, the prevention and treatment of CVD have been a global focus since CVD is the number one cause of mortality and morbidity. In the pathogenesis of CVD, it was generally thought that impaired cholesterol homeostasis might be a risk factor. Cholesterol homeostasis is affected by exogenous factors (i.e. diet) and endogenous factors (i.e. certain receptors, enzymes and transcription factors). In this context, the number of studies investigating the potential mechanisms of dietary fatty acids on cholesterol homeostasis have increased in recent years. As well, the cluster of differentiation 36 (CD36) receptor is a multifunctional membrane receptor involved in fatty acid uptake, lipid metabolism, atherothrombosis and inflammation. CD36 is proposed to be a crucial molecule for cholesterol homeostasis in various mechanisms including absorption/reabsorption, synthesis, and transport of cholesterol and bile acids. Moreover, it has been reported that the amount of fatty acids and fatty acid pattern of the diet influence the CD36 level and CD36-mediated cholesterol metabolism principally in the liver, intestine and macrophages. In these processes, CD36-mediated cholesterol and lipoprotein homeostasis might be impaired by dietary SFA and trans-fatty acids, whereas ameliorated by MUFA in the diet. The effects of PUFA on CD36-mediated cholesterol homeostasis are controversial depending on the amount of n-3 PUFA and n-6 PUFA, and the n-3:n-6 PUFA ratio. Thus, since the CD36 receptor is suggested to be a novel nutrient-sensitive biomarker, the role of CD36 and dietary fatty acids in cholesterol metabolism might be considered in medical nutrition therapy in the near future. Therefore, the novel nutritional target of CD36 and interventions that focus on dietary fatty acids and potential mechanisms underlying cholesterol homeostasis are discussed in this review.

scholarly journals Evidence that the entire Golgi apparatus cycles in interphase HeLa cells

2001 ◽  
Vol 155 (4) ◽  
pp. 543-556 ◽  
Author(s):  
Suzanne Miles ◽  
Heather McManus ◽  
Kimberly E. Forsten ◽  
Brian Storrie
Keyword(s):  
Membrane Proteins ◽  
Golgi Apparatus ◽  
Mammalian Cells ◽  
Dynamic Structure ◽  
Dominant Negative ◽  
Integral Membrane Proteins ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Golgi Region ◽  
Exit Block

We tested whether the entire Golgi apparatus is a dynamic structure in interphase mammalian cells by assessing the response of 12 different Golgi region proteins to an endoplasmic reticulum (ER) exit block. The proteins chosen spanned the Golgi apparatus and included both Golgi glycosyltransferases and putative matrix proteins. Protein exit from ER was blocked either by microinjection of a GTP-restricted Sar1p mutant protein in the presence of a protein synthesis inhibitor, or by plasmid-encoded expression of the same dominant negative Sar1p. All Golgi region proteins examined lost juxtanuclear Golgi apparatus–like distribution as scored by conventional and confocal fluorescence microscopy in response to an ER exit block, albeit with a differential dependence on Sar1p concentration. Redistribution of GalNAcT2 was more sensitive to low Sar1pdn concentrations than giantin or GM130. Redistribution was most rapid for p27, COPI, and p115. Giantin, GM130, and GalNAcT2 relocated with approximately equal kinetics. Distinct ER accumulation could be demonstrated for all integral membrane proteins. ER-accumulated Golgi region proteins were functional. Photobleaching experiments indicated that Golgi-to-ER protein cycling occurred in the absence of any ER exit block. We conclude that the entire Golgi apparatus is a dynamic structure and suggest that most, if not all, Golgi region–integral membrane proteins cycle through ER in interphase cells.

scholarly journals Integral Membrane Proteins of the Nuclear Envelope Are Dispersed throughout the Endoplasmic Reticulum during Mitosis

1997 ◽  
Vol 137 (6) ◽  
pp. 1199-1210 ◽  
Author(s):  
Li Yang ◽  
Tinglu Guan ◽  
Larry Gerace
Keyword(s):  
Membrane Proteins ◽  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Mammalian Cells ◽  
Polyclonal Antibodies ◽  
Integral Membrane Proteins ◽  
Immunogold Electron Microscopy ◽  
Nuclear Pore ◽  
Nuclear Lamins ◽  
Nuclear Membranes

We have analyzed the fate of several integral membrane proteins of the nuclear envelope during mitosis in cultured mammalian cells to determine whether nuclear membrane proteins are present in a vesicle population distinct from bulk ER membranes after mitotic nuclear envelope disassembly or are dispersed throughout the ER. Using immunofluorescence staining and confocal microscopy, we compared the localization of two inner nuclear membrane proteins (laminaassociated polypeptides 1 and 2 [LAP1 and LAP2]) and a nuclear pore membrane protein (gp210) to the distribution of bulk ER membranes, which was determined with lipid dyes (DiOC6 and R6) and polyclonal antibodies. We found that at the resolution of this technique, the three nuclear envelope markers become completely dispersed throughout ER membranes during mitosis. In agreement with these results, we detected LAP1 in most membranes containing ER markers by immunogold electron microscopy of metaphase cells. Together, these findings indicate that nuclear membranes lose their identity as a subcompartment of the ER during mitosis. We found that nuclear lamins begin to reassemble around chromosomes at the end of mitosis at the same time as LAP1 and LAP2 and propose that reassembly of the nuclear envelope at the end of mitosis involves sorting of integral membrane proteins to chromosome surfaces by binding interactions with lamins and chromatin.

scholarly journals Characterization of constitutive ER-phagy of excess membrane proteins

PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009255
Author(s):  
Zhanna Lipatova ◽  
Valeriya Gyurkovska ◽  
Sarah F. Zhao ◽  
Nava Segev
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Human Health ◽  
Mammalian Cells ◽  
Normal Growth ◽  
Integral Membrane Proteins ◽  
Yeast Cells ◽  
Cellular Proteins

Thirty percent of all cellular proteins are inserted into the endoplasmic reticulum (ER), which spans throughout the cytoplasm. Two well-established stress-induced pathways ensure quality control (QC) at the ER: ER-phagy and ER-associated degradation (ERAD), which shuttle cargo for degradation to the lysosome and proteasome, respectively. In contrast, not much is known about constitutive ER-phagy. We have previously reported that excess of integral-membrane proteins is delivered from the ER to the lysosome via autophagy during normal growth of yeast cells. Whereas endogenously expressed ER resident proteins serve as cargos at a basal level, this level can be induced by overexpression of membrane proteins that are not ER residents. Here, we characterize this pathway as constitutive ER-phagy. Constitutive and stress-induced ER-phagy share the basic macro-autophagy machinery including the conserved Atgs and Ypt1 GTPase. However, induction of stress-induced autophagy is not needed for constitutive ER-phagy to occur. Moreover, the selective receptors needed for starvation-induced ER-phagy, Atg39 and Atg40, are not required for constitutive ER-phagy and neither these receptors nor their cargos are delivered through it to the vacuole. As for ERAD, while constitutive ER-phagy recognizes cargo different from that recognized by ERAD, these two ER-QC pathways can partially substitute for each other. Because accumulation of membrane proteins is associated with disease, and constitutive ER-phagy players are conserved from yeast to mammalian cells, this process could be critical for human health.

scholarly journals Characterization of Constitutive macro-ER-phagy

2020 ◽  
Author(s):  
Zhanna Lipatova ◽  
Valeriya Gyurkovska ◽  
Sarah F. Zhao ◽  
Nava Segev
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Proteins ◽  
Er Stress ◽  
Mammalian Cells ◽  
Normal Growth ◽  
Integral Membrane Proteins ◽  
Yeast Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

AbstractThirty percent of all cellular proteins are inserted into the endoplasmic reticulum (ER), which spans throughout the cytoplasm. Two well-established stress-induced pathways ensure quality control (QC) at the ER: ER-phagy and ER-associated degradation (ERAD), which shuttle cargo for degradation to the lysosome and proteasome, respectively. In contrast, not much is known about constitutive ER-phagy. We have previously reported that excess of integral-membrane proteins is delivered from the ER to the lysosome via autophagy during normal growth of yeast cells. Here, we characterize this pathway as constitutive ER-phagy. Constitutive and stress-induced ER-phagy share the basic macro-autophagy machinery including the conserved Atgs and Ypt1 GTPase. However, induction of stress-induced autophagy is not needed for constitutive ER-phagy to occur. Moreover, the selective receptors needed for starvation-induced ER-phagy, Atg39 and Atg40, are not required for constitutive ER-phagy and neither these receptors nor their cargos are delivered through it to the vacuole. As for ERAD, while constitutive ER-phagy recognizes cargo different from that recognized by ERAD, these two ER-QC pathways can partially substitute for each other. Because accumulation of membrane proteins is associated with disease, and constitutive ER-phagy players are conserved from yeast to mammalian cells, this process could be critical for human health.Author SummaryAccumulation of excess proteins can lead to their aggregation, which in turn can cause multiple disorders, notably neurodegenerative disease. Nutritional and endoplasmic-reticulum (ER) stress stimulate autophagy and ER-associated degradation (ERAD) to clear excess and misfolded proteins, respectively. However, not much is known about clearance of excess proteins during normal growth. We have previously shown that excess integral-membrane proteins are cleared from the ER by macro-autophagy during normal growth of yeast cells. Here we characterize this pathway as constitutive ER-phagy. While this pathway shares machinery of core Atgs and autophagosomes with nutritional stress-induced ER-phagy, it differs from the latter: It is independent of the stress response and of receptors needed for stress-induced ER-phagy, and while stress-induced ER-phagy is not discriminatory, constitutive ER-phagy has specific cargos. However, when constitutive ER-phagy fails, machinery specific to stress-induced ER-phagy can process its cargo. Moreover, constitutive ER-phagy is also not dependent on ER-stress or the unfolded protein response (UPR) stimulated by this stress, although its failure elicits UPR. Finally, constitutive ER-phagy and ERAD can partially process each other’s cargo upon failure. In summary, constitutive ER-phagy, which clears excess integral-membrane proteins from the ER during normal growth does not require nutritional or ER stress for its function.

AMP Kinase-Induced Skeletal Muscle Glucose But Not Long-Chain Fatty Acid Uptake Is Dependent on Nitric Oxide

Diabetes ◽  
2004 ◽  
Vol 53 (6) ◽  
pp. 1429-1435 ◽  
Author(s):  
J. Shearer ◽  
P. T. Fueger ◽  
B. Vorndick ◽  
D. P. Bracy ◽  
J. N. Rottman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Chain Fatty Acid ◽  
Acid Uptake ◽  
Amp Kinase ◽  
Long Chain Fatty Acid ◽  
Long Chain

scholarly journals Fatty-Acid Uptake in Prostate Cancer Cells Using Dynamic Microfluidic Raman Technology

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1652
Author(s):  
Nga-Tsing Tang ◽  
Richard D. Snook ◽  
Mick D. Brown ◽  
Bryan A. Haines ◽  
Andrew Ridley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Fatty Acid ◽  
Cancer Progression ◽  
Nile Red ◽  
Experimental System ◽  
Fatty Acid Uptake ◽  
Microfluidic System ◽  
Acid Uptake ◽  
Lipid Uptake ◽  
Omega 3

It is known that intake of dietary fatty acid (FA) is strongly correlated with prostate cancer progression but is highly dependent on the type of FAs. High levels of palmitic acid (PA) or arachidonic acid (AA) can stimulate the progression of cancer. In this study, a unique experimental set-up consisting of a Raman microscope, coupled with a commercial shear-flow microfluidic system is used to monitor fatty acid uptake by prostate cancer (PC-3) cells in real-time at the single cell level. Uptake of deuterated PA, deuterated AA, and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were monitored using this new system, while complementary flow cytometry experiments using Nile red staining, were also conducted for the validation of the cellular lipid uptake. Using this novel experimental system, we show that DHA and EPA have inhibitory effects on the uptake of PA and AA by PC-3 cells.

Impact of in Vitro Fatty Acid Uptake on Nitric Oxide Production and Antilisterial Activity of WEHI-3 Cells

1996 ◽  
Vol 797 (1 Microbial Pat) ◽  
pp. 296-298 ◽  
Author(s):  
U. S. BABU ◽  
P. L. WIESENFELD ◽  
V. K. BUNNING ◽  
R. B. RAYBOURNE
Keyword(s):  
Nitric Oxide ◽  
Fatty Acid ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Nitric Oxide Production ◽  
Oxide Production
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