EVs as Pathogenic Mediators in NASH Cells release diverse types of membrane-bound extracellular vesicles into the extracellular milieu. These can be further classified into three main subgroups based on their cellular biogenesis: exosomes, microvesicles, and apoptotic bodies.21 Exosomes (~50-100 nm diameter) originate from the multivesicular body (MVB); MVBs are well-characterized endosomal precursors of the lysosomal degradation pathway. MVBs can also fuse with the plasma membrane. In this case, their intraluminal vesicle contents are released into the extracellular space; thus becoming “exosomes”.22 Microvesicles (~50-1000 nm diameter) bud directly from the plasma membrane. Apoptotic bodies (more than 500 nm in diameter) represent …show more content…
One of the early reports of their role in an animal model of NASH was the observation that adoptive transfer of EVs isolated from the serum of high fat diet-fed mice into chow diet-fed mice results in immature myeloid cells activation and homing to the liver, which was associated with increased levels of hepatic proinflammatory markers and serum aminotransferases.32 Subsequent reports demonstrated a significant increase in the release of EVs from hepatocytes upon treatment with lipids such as palmitate and its active metabolite lysophosphatidylcholine (LPC),27 28 33 toxic lipid-induced EV release by hepatocytes was observed across different species.28 EVs derived from hepatocyte under lipotoxic stress are heterogeneous regarding their biogenesis, selected cargo, release, and intended target cells. For example, LPC-induced EV release is mediated by the stress kinase mixed lineage kinase 3 (MLK3).33 Furthermore, MLK3 regulates the chemotactic cargo of the EVs. Genetic or pharmacological inhibition of MLK3 results in a reduced abundance of the potent C-X-C motif chemokine ligand 10 (CXCL10) in vesicles derived from LPC-treated hepatocytes.33 Likewise, MLK3-/- mice fed a NASH-inducing diet34 have reduced CXCL10 levels in their plasma EVs. This, in turn, is
Fig. 12 CXL10-/- mice are relatively protected against FFC-induced liver injury and inflammation. WT & CXCL10-/- mice were fed either chow or FFC-diet for 20 weeks. (A) Plasma alanine aminotransferase (ALT) levels were measured. (C) Total RNA was extracted from liver tissue and mRNA expression of surface macrophage marker cluster of differentiation (CD)68 was evaluated by real-time qPCR. (D) Assessment of macrophage infiltration in fixed liver tissue was done by immunohistochemistry using macrophage galactose-specific lectin (Mac-2) antibody. Bar columns represent mean ± S.E.M. *** P < .001, * P < .05 compared to WT chow-fed mice.
BSP, S. (2010). How is EM different from light microscopy? Retrieved April 25, 2015, from http://bsp.med.harvard.edu/node/222
Proteus vulgaris was discovered to be the unknown organism after several tests were concluded. First, a gram stain was done to determine if the unknown was gram negative or gram positive. It turned out to be a gram negative organism, so further tests were ordered based on this fact. The tests included were a OF glucose test, a Citrate test, a SIM test, and also a Urease test. The OF glucose test came out positive for a strict fermenter because both tubes turned yellow. The Citrate test came out negative because there was no color change identified. The SIM test showed positive for Sulfur, Indole, and motility. The black precipitate that formed shows the production of H2S and the red color after the Kovács reagent was added indicates Indole
Thus, there is an urgency to evaluate the effects of immune response on APAP toxicity using a human KCs and hepatocyte co-culture system. Since a 3D multicellular system containing hepatocytes and other non-hepatocytes can better reflect the cell-cell interactions of a real situation [11], in this study, we used the 3D liver microtissues consisting of primary human hepatocytes (PHH) and KCs (1 : 1) to study the inflammation-mediated hepatotoxicity after acetaminophen overdose.
The early endosomes progress gradually. The early endosomes transform into the late endosomes because of the lowered levels of ph, when Rab proteins are traded, and the earlier endosomes internal structure has a crucial
The catecholamines consist of norepinephrine and epinephrine, and their role is activate B-adrenergic receptors (βARs) to increase cAMP levels and cAMP-dependent protein kinase A (PKA) activity. This phosphorylation stimulates the release of adipose energy stores due to lipolysis (the hydrolysis of triglycerides) and the liberation of free fatty acids. Insulin is the opposing metabolic regulator that antagonizes the action of catecholamines to stimulate lipolysis by activating phosphodiesterases that degrade cAMP and by using the protein kinase AKT to activate lipid synthesis pathways to promote energy
Type II Diabetes is a chronic metabolic disease linked to obesity (Singla et al. 2010). Adipocytes produce several hormones and cytokines, including those that regulate metabolism and inflammatory responses in the body (Singla et al. 2010). Obese individuals characteristically have excess adipose tissue, which results in the overproduction of these signalling molecules, disturbing communication pathways. (Singla et al. 2010). For example, non-essential fatty acids (NEFAs) and the hormone resistin, both secreted by adipose tissue, are overproduced by obese individuals; excess NEFAs and resistin results in suppression of insulin activity in metabolic pathways, decreasing glucose tolerance (Singla et al. 2010) (Kahn et al. 2006). Pro-inflammatory cytokines produced by adipocytes, including tumour necrosis factor-α (TNF-α)
the pathogensis of insulin resistance greatly linked to adipose tissue. intra-abdominal fat cells release free fatty acids and other adipocytokines which produce an inflammatory response and could have
Aerobes use gaseous oxygen for metabolism and process enzymes that are need to eliminate the toxic oxygen byproducts. An organism that cannot grow without oxygen is called an obligate aerobe. A facultative aerobe is an organism that does not require oxygen for metabolism, but is capable of growing without oxygen. Microaerophiles do not grow at normal atmospheric oxygen because they only need small amounts. An anaerobe is a microorganism that lacks metabolic enzymes needed for respiration. Aerotolerant anaerobes do not use oxygen gas but can survive and grow in its presence.
Microvesicles are released by exocytosis through a mechanism dependent on cytoskeleton activation and under the regulation of p53 protein. This release is enhanced by different environmental stimuli like oxidative stress, injury or hypoxia.
Upon binding the virus enters human cells via receptor-mediated endocytosis and forms a vesicle known as an endosome.
Endocytosis is the capacity to disguise material from outside the cell is critical for a few cell forms including the ingestion of fundamental supplements, expulsion of dead or harmed cells from the body, and guard against microorganisms. Eukaryotic cells disguise liquid, extensive and little particles, and even different cells from their surroundings by a procedure called endocytosis. Amid endocytosis, the plasma layer of the cell frames a pocket around the material to be disguised. The pocket closes and afterward isolates from within surface of the plasma layer to shape a film encased air pocket, or vesicle, containing the ingested
Aim 2: Identify functions of IP6K1 in lipolysis. K1-KO mice exhibit enhanced fasting induced weight loss. They also display enhanced basal lipolysis and downregulation of the lipolytic modulator perilipin1 (PLIN1) in the adipose tissues. IP6K1 possesses a lipase motif by which it binds and stabilizes PLIN1. PKA (Protein kinase A) phosphorylates IP6K1 especially during -adrenergic receptor (-AR)
Early endosomes suffer several modifications and mature to late endosomes. This process and its molecular players are not completely known yet. When LEs mature, there is a dramatic remodeling of the endosome: they become larger, membrane-bound receptors are sorted into internal vesicles, their associated machinery is changed and they move faster towards the nucleus of the cell (Collinet et al, 2010).
Endosomal multivesicular bodies (MVBs) can either fuse with lysosomes for degradation of unwanted materials or work as storage for MHC class II molecules in dendritic cells. MVBs can also fuse with plasma membrane, resulting in the release of vesicles called exosomes into the extracellular environment as a carrier destined for simulations, since exosomes can be taken up by other cells via phagocytosis. Various cell types such as hematopoietic cells, mast cells and lymphocytes undergo the same mechanism in order to release exosomes. (Keller et al., 2006)