FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2233732181> ?p ?o ?g. }

• W2233732181 abstract "OF DISSERTATION NOVEL INSIGHTS INTO THE FUNCTION AND RGULATION OF GROUP X SECRETORY PHOSPOLIPASE A2 Group X secretory phospholipase A2 (GX sPLA2) hydrolyzes membrane phospholipids producing free fatty acids and lysophospholipids. Previous studies from our lab suggest that mice with targeted deletion of GX sPLA2 (GX KO) have increased age-related weight gain due to an increase in overall adiposity. Paradoxically, this increased adiposity is associated with improved age-related glucose intolerance. GX KO mice also demonstrate a reduced inflammatory response to lipopolysaccharide injection. In vitro studies indicate this phenotype may be attributable to blunted macrophage mediated inflammatory responses. Given the role of macrophages in promoting adipose tissue (AT) inflammation and metabolic dysfunction in response to diet-induced obesity, we hypothesized that GX KO mice would be protected from the obesity related metabolic derangements associated with overfeeding. Unexpectedly, GX KO mice were only partially protected from high fat (HFD) diet-induced glucose intolerance and showed no improvement in HFD-induced insulin resistance. Moreover, GX KO mice were not protected against HFD-induced AT inflammation. GX sPLA2 is produced as a proenzyme (pro-GX sPLA2), and propeptide cleavage is required for enzymatic activity. Furin-like proprotein convertases (PCs) have recently been implicated in the proteolytic activation of pro-GX sPLA2; however the identity of individual PCs involved is unclear. Previous findings from our lab have shown that GX sPLA2 is expressed in the adrenals where it regulates glucocorticoid production. GX KO mice have increased plasma corticosterone levels under both basal and ACTH-induced stress conditions. However, how GX sPLA2 is regulated in the adrenals is still uncertain. We hypothesized that PCs may be involved in the proteolytic activation of pro-GX sPLA2 in the adrenals. Here we report the novel findings that the PCs, furin and PCSK6, proteolytically activate pro-GX sPLA2 in Y1 adrenal cells. Furthermore, we demonstrate that PC dependent processing of pro-GX sPLA2 is necessary for GX sPLA2 dependent suppression of steroidogenesis. Finally, we provide evidence that pro-GX sPLA2 processing by PCs is enhanced in response to adrenocorticotropic hormone (ACTH), suggesting a novel mechanism for negatively regulating adrenal steroidogenesis. Cumulatively, these studies provide valuable insight into the function and regulation of GX sPLA2." @default.
• W2233732181 created "2016-06-24" @default.
• W2233732181 creator A5077423873 @default.
• W2233732181 creator A5082849723 @default.
• W2233732181 date "2013-01-01" @default.
• W2233732181 modified "2023-09-27" @default.
• W2233732181 title "Novel insights into the function and regulation of group X secretory phospholipase A 2" @default.
• W2233732181 cites W114652413 @default.
• W2233732181 cites W1507135964 @default.
• W2233732181 cites W1514236298 @default.
• W2233732181 cites W1545152283 @default.
• W2233732181 cites W1554348499 @default.
• W2233732181 cites W1577692113 @default.
• W2233732181 cites W1588740678 @default.
• W2233732181 cites W1601462184 @default.
• W2233732181 cites W1624744767 @default.
• W2233732181 cites W1638473681 @default.
• W2233732181 cites W1680099832 @default.
• W2233732181 cites W1773423156 @default.
• W2233732181 cites W181695750 @default.
• W2233732181 cites W1937327614 @default.
• W2233732181 cites W1942154801 @default.
• W2233732181 cites W1964651041 @default.
• W2233732181 cites W1965152120 @default.
• W2233732181 cites W1965574341 @default.
• W2233732181 cites W1967734914 @default.
• W2233732181 cites W1968008704 @default.
• W2233732181 cites W1970898912 @default.
• W2233732181 cites W1971986721 @default.
• W2233732181 cites W1972235985 @default.
• W2233732181 cites W1974196308 @default.
• W2233732181 cites W1975150752 @default.
• W2233732181 cites W1975537939 @default.
• W2233732181 cites W1976477866 @default.
• W2233732181 cites W1977873926 @default.
• W2233732181 cites W1979249143 @default.
• W2233732181 cites W1980462986 @default.
• W2233732181 cites W1985929369 @default.
• W2233732181 cites W1988997346 @default.
• W2233732181 cites W1989036330 @default.
• W2233732181 cites W1990318022 @default.
• W2233732181 cites W1990807902 @default.
• W2233732181 cites W1991136318 @default.
• W2233732181 cites W1992641427 @default.
• W2233732181 cites W1992809091 @default.
• W2233732181 cites W1993067007 @default.
• W2233732181 cites W1993851066 @default.
• W2233732181 cites W1994346346 @default.
• W2233732181 cites W1994395273 @default.
• W2233732181 cites W1998128012 @default.
• W2233732181 cites W2003432885 @default.
• W2233732181 cites W2003838989 @default.
• W2233732181 cites W2004147452 @default.
• W2233732181 cites W2006990725 @default.
• W2233732181 cites W2007715713 @default.
• W2233732181 cites W2008329655 @default.
• W2233732181 cites W2010911569 @default.
• W2233732181 cites W2011209855 @default.
• W2233732181 cites W2011255130 @default.
• W2233732181 cites W2011653215 @default.
• W2233732181 cites W2012295774 @default.
• W2233732181 cites W2014749976 @default.
• W2233732181 cites W2014867833 @default.
• W2233732181 cites W2015095702 @default.
• W2233732181 cites W2015170595 @default.
• W2233732181 cites W2015270219 @default.
• W2233732181 cites W2015491565 @default.
• W2233732181 cites W2015747541 @default.
• W2233732181 cites W2016512598 @default.
• W2233732181 cites W2021170260 @default.
• W2233732181 cites W2022042899 @default.
• W2233732181 cites W2022674779 @default.
• W2233732181 cites W2022759858 @default.
• W2233732181 cites W2024218255 @default.
• W2233732181 cites W2028105030 @default.
• W2233732181 cites W2029245407 @default.
• W2233732181 cites W2031855575 @default.
• W2233732181 cites W2032435199 @default.
• W2233732181 cites W2032986550 @default.
• W2233732181 cites W2033981821 @default.
• W2233732181 cites W2034770942 @default.
• W2233732181 cites W2034904195 @default.
• W2233732181 cites W2037438579 @default.
• W2233732181 cites W2037838520 @default.
• W2233732181 cites W2038569244 @default.
• W2233732181 cites W2039379186 @default.
• W2233732181 cites W2040186280 @default.
• W2233732181 cites W2043829287 @default.
• W2233732181 cites W2044399712 @default.
• W2233732181 cites W2045147217 @default.
• W2233732181 cites W2045786048 @default.
• W2233732181 cites W2046663739 @default.
• W2233732181 cites W2048134681 @default.
• W2233732181 cites W2051243229 @default.
• W2233732181 cites W2057486586 @default.
• W2233732181 cites W2058479383 @default.
• W2233732181 cites W2060632291 @default.
• W2233732181 cites W2061413962 @default.
• W2233732181 cites W2061725840 @default.
• W2233732181 cites W2061962280 @default.

• next