FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384298089> ?p ?o ?g. }

• W4384298089 abstract "The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice. Inflammation disrupts the TCA cycle at the level of succinate dehydrogenase (SDH), leading to succinate accumulation and disturbed steroidogenesis. Mechanistically, IL-1β reduces SDHB expression through upregulation of DNA methyltransferase 1 (DNMT1) and methylation of the SDHB promoter. Consequently, increased succinate levels impair oxidative phosphorylation and ATP synthesis and enhance ROS production, leading to reduced steroidogenesis. Together, we demonstrate that the IL-1β-DNMT1-SDHB-succinate axis disrupts steroidogenesis. Our findings not only provide a mechanistic explanation for adrenal dysfunction in severe inflammation, but also offer a potential target for therapeutic intervention." @default.
• W4384298089 created "2023-07-15" @default.
• W4384298089 creator A5004023214 @default.
• W4384298089 creator A5016302235 @default.
• W4384298089 creator A5019412191 @default.
• W4384298089 creator A5024387900 @default.
• W4384298089 creator A5024429162 @default.
• W4384298089 creator A5025650360 @default.
• W4384298089 creator A5026685270 @default.
• W4384298089 creator A5029679652 @default.
• W4384298089 creator A5034287499 @default.
• W4384298089 creator A5035750809 @default.
• W4384298089 creator A5037003034 @default.
• W4384298089 creator A5049689971 @default.
• W4384298089 creator A5051830785 @default.
• W4384298089 creator A5059536565 @default.
• W4384298089 creator A5067860976 @default.
• W4384298089 creator A5074211261 @default.
• W4384298089 creator A5085234810 @default.
• W4384298089 creator A5086512193 @default.
• W4384298089 creator A5086672334 @default.
• W4384298089 creator A5088211617 @default.
• W4384298089 date "2023-07-14" @default.
• W4384298089 modified "2023-10-17" @default.
• W4384298089 title "Succinate mediates inflammation-induced adrenocortical dysfunction" @default.
• W4384298089 cites W1818595191 @default.
• W4384298089 cites W1969024223 @default.
• W4384298089 cites W1975240351 @default.
• W4384298089 cites W1975556592 @default.
• W4384298089 cites W1977023380 @default.
• W4384298089 cites W1982702913 @default.
• W4384298089 cites W1983521123 @default.
• W4384298089 cites W1984053258 @default.
• W4384298089 cites W2007130516 @default.
• W4384298089 cites W2012443484 @default.
• W4384298089 cites W2018289835 @default.
• W4384298089 cites W2023771004 @default.
• W4384298089 cites W2036897871 @default.
• W4384298089 cites W2037536401 @default.
• W4384298089 cites W2047162021 @default.
• W4384298089 cites W2048938503 @default.
• W4384298089 cites W2057199368 @default.
• W4384298089 cites W2057631938 @default.
• W4384298089 cites W2092257934 @default.
• W4384298089 cites W2100837269 @default.
• W4384298089 cites W2114970231 @default.
• W4384298089 cites W2126846194 @default.
• W4384298089 cites W2130410032 @default.
• W4384298089 cites W2134526812 @default.
• W4384298089 cites W2138436127 @default.
• W4384298089 cites W2146693123 @default.
• W4384298089 cites W2149282639 @default.
• W4384298089 cites W2152239989 @default.
• W4384298089 cites W2156618518 @default.
• W4384298089 cites W2160833615 @default.
• W4384298089 cites W2169456326 @default.
• W4384298089 cites W2193258608 @default.
• W4384298089 cites W2206617731 @default.
• W4384298089 cites W2214074259 @default.
• W4384298089 cites W2320349682 @default.
• W4384298089 cites W2422535565 @default.
• W4384298089 cites W2429977049 @default.
• W4384298089 cites W2460752692 @default.
• W4384298089 cites W2484033988 @default.
• W4384298089 cites W2522038806 @default.
• W4384298089 cites W2588385654 @default.
• W4384298089 cites W2624067357 @default.
• W4384298089 cites W2787897791 @default.
• W4384298089 cites W2799743239 @default.
• W4384298089 cites W2884967473 @default.
• W4384298089 cites W2886831287 @default.
• W4384298089 cites W2892227414 @default.
• W4384298089 cites W2941375729 @default.
• W4384298089 cites W2949093503 @default.
• W4384298089 cites W2949185749 @default.
• W4384298089 cites W2967886676 @default.
• W4384298089 cites W2981571928 @default.
• W4384298089 cites W2991106430 @default.
• W4384298089 cites W2994179930 @default.
• W4384298089 cites W3000456443 @default.
• W4384298089 cites W3000772496 @default.
• W4384298089 cites W3003556593 @default.
• W4384298089 cites W3006107828 @default.
• W4384298089 cites W3009532008 @default.
• W4384298089 cites W3016117371 @default.
• W4384298089 cites W3036126029 @default.
• W4384298089 cites W3039148410 @default.
• W4384298089 cites W3093397681 @default.
• W4384298089 cites W3093706465 @default.
• W4384298089 cites W3100471102 @default.
• W4384298089 cites W3108232640 @default.
• W4384298089 cites W3125441563 @default.
• W4384298089 cites W3162482903 @default.
• W4384298089 cites W3171653527 @default.
• W4384298089 cites W3176744270 @default.
• W4384298089 cites W3212294567 @default.
• W4384298089 cites W3215897154 @default.
• W4384298089 cites W4210670345 @default.
• W4384298089 cites W4220700063 @default.
• W4384298089 cites W4230096730 @default.

• next