Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipids may serve as coupling factors in K(ATP)-independent glucose sensing in beta-cells. We have previously demonstrated that beta-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether beta-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an acylglyceride-derived coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS, an effect proposed to be due to activation of a lipase. In perifused islets, orlistat attenuated mainly the second phase of insulin secretion. Because the rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar were unaffected by orlistat whereas the second phase of insulin secretion was reduced, it seems likely that a lipid coupling factor involved in K(ATP)-independent glucose sensing has been perturbed. Thus, beta-cell lipase activity is involved in GSIS, emphasizing the important role of beta-cell lipid metabolism for insulin secretion.
 ...
PMID:Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion. 1469 6

Lipids have been implicated in beta-cell stimulus-secretion coupling. In such a role, lipases in beta-cells would be required to generate lipid coupling factors. We have shown previously that glucose stimulates lipolysis in rodent islets. In addition, lipolysis and diacylglycerol lipase activity in islets are abolished by orlistat, an irreversible lipase inhibitor with a broad specificity for substrates. Moreover, orlistat dose-dependently inhibits glucose- and forskolin-stimulated insulin secretion, while leaving glucose oxidation and the rise in the ATP/ADP ratio intact. In an effort to identify beta-cell lipase(s), we found that HSL (hormone-sensitive lipase), the rate-limiting enzyme for acylglycerol hydrolysis in adipocytes, is expressed in rodent beta-cells. To resolve the role of this lipase, we have created global and beta-cell-specific knockout mice. Although our line of global HSL-knockout mice is moderately glucose-intolerant owing to reduced peripheral insulin sensitivity and exhibits normal islet metabolism and insulin secretion, other HSL-knockout lines have displayed impaired insulin secretion under certain conditions. In contrast, beta-cell-specific HSL-knockout mice, which are less prone to genetic redundancy, are hyperglycaemic, presumably caused by a perturbation of first-phase insulin secretion. Thus studies by us and others demonstrate that lipases, such as HSL, play a regulatory role in beta-cell stimulus-secretion coupling.
 ...
PMID:Lipases in the pancreatic beta-cell: implications for insulin secretion. 1879 56

Growth inhibition in acid soils due to Al stress affects crop production worldwide. To understand mechanisms in sensitive crops that are affected by Al stress, a proteomic analysis of primary tomato root tissue, grown in Al-amended and non-amended liquid cultures, was performed. DIGE-SDS-MALDI-TOF-TOF analysis of these tissues resulted in the identification of 49 proteins that were differentially accumulated. Dehydroascorbate reductase, glutathione reductase, and catalase enzymes associated with antioxidant activities were induced in Al-treated roots. Induced enzyme proteins associated with detoxification were mitochondrial aldehyde dehydrogenase, catechol oxidase, quinone reductase, and lactoylglutathione lyase. The germin-like (oxalate oxidase) proteins, the malate dehydrogenase, wali7 and heavy-metal associated domain-containing proteins were suppressed. VHA-ATP that encodes for the catalytic subunit A of the vacuolar ATP synthase was induced and two ATPase subunit 1 isoforms were suppressed. Several proteins in the active methyl cycle, including SAMS, quercetin 3-O-methyltransferase and AdoHcyase, were induced by Al stress. Other induced proteins were isovaleryl-CoA dehydrogenase and the GDSL-motif lipase hydrolase family protein. NADPH-dependent flavin reductase and beta-hydroxyacyl-ACP dehydratase were suppressed.
 ...
PMID:Proteome changes induced by aluminium stress in tomato roots. 1982 Mar 57

Powdery mildews are biotrophic pathogens causing fungal diseases in many economically important crops, including cereals, which are affected by Blumeria graminis. Powdery mildews only invade the epidermal cell layer of leaf tissues, in which they form haustorial structures. Haustoria are at the center of the biotrophic interaction by taking up nutrients from the host and by delivering effectors in the invaded cells to jeopardize plant immunity. Haustoria are composed of a fungal core delimited by a haustorial plasma membrane and cell wall. Surrounding these is the extrahaustorial complex, of which the extrahaustorial membrane is of plant origin. Although haustoria transcriptomes and proteomes have been investigated for Blumeria, the proteomes of barley epidermis upon infection and the barley components of the extrahaustorial complex remains unexplored. When comparing proteomes of infected and non-infected epidermis, several classical pathogenesis-related (PR) proteins were more abundant in infected epidermis. These included peroxidases, chitinases, cysteine-rich venom secreted proteins/PR1 and two thaumatin-like PR5 protein isoforms, of which TLP5 was previously shown to interact with the Blumeria effector BEC1054 (CSEP0064). Against expectations, transient TLP5 gene silencing suggested that TLP5 does not contribute to resistance but modulates susceptibility towards B. graminis. In a second proteomics comparison, haustorial structures were enriched from infected epidermal strips to identify plant proteins closely associated with the extrahaustorial complex. In these haustoria-enriched samples, relative abundances were higher for several V-type ATP synthase/ATPase subunits, suggesting the generation of proton gradients in the extrahaustorial space. Other haustoria-associated proteins included secreted or membrane proteins such as a PIP2 aquaporin, an early nodulin-like protein 9, an aspartate protease and other proteases, a lipase, and a lipid transfer protein, all of which are potential modulators of immunity, or the targets of pathogen effectors. Moreover, the ER BIP-like HSP70, may link ER stress responses and the idea of ER-like properties previously attributed to the extrahaustorial membrane. This initial investigation exploring the barley proteomes of Blumeria-infected tissues and haustoria, associated with a transient gene silencing approach, is invaluable to gain first insight of key players of resistance and susceptibility.
 ...
PMID:Analysis of Barley Leaf Epidermis and Extrahaustorial Proteomes During Powdery Mildew Infection Reveals That the PR5 Thaumatin-Like Protein TLP5 Is Required for Susceptibility Towards Blumeria graminis f. sp. hordei. 3173 84

Ureteropelvic junction (UPJ) obstruction is a common problem in children, but its etiology remains unclear. In this study, the proteome profiles of the obstructed segment and its surrounding distal and proximal parts were comparatively evaluated. Twelve children younger than 2 years of age with unilateral intrinsic UPJ obstruction were included. The excised operational tissue was divided into three parts immediately after resection: the obstructed part (Obst), the distal normal ureteral part (Dist), and the proximal part of the obstructed segment (Prox). Proteins extracted from the tissue samples were subjected to two-dimensional gel electrophoresis analysis to identify differentially regulated proteins. Spot analysis revealed that four proteins, namely tropomyosin beta and alpha-1 chains, actin and desmin, were upregulated in Obst in comparison to Dist. A similar analysis between Obst and Prox showed that heat shock protein beta-1 and carbonic anhydrase-1 were upregulated in Obst, while tropomyosin alpha 3 chain and ATP synthase beta were upregulated in Prox. The last comparative analysis between Dist and Prox revealed upregulation of annexin-A5 and annexin-A1 in Dist and vimentin, mitochondrial ATP synthase subunit-beta, peroxiredoxin-2, and apolipoprotein-A1 in Prox. Bioinformatics analysis using the STRING server indicated that the differentially regulated proteins, altogether, point to the changes occurring in muscle filament sliding pathway. When regulations occurring in each group were mutually compared, a change in lipase inhibition activity was detected by STRING. This is the first study scrutinizing changes occurring in protein profiles in UPJ.
 ...
PMID:Comparative Proteome Analyses of Ureteropelvic Junction Obstruction and Surrounding Ureteral Tissue. 3225 13