Matches in SemOpenAlex for { <https://semopenalex.org/work/W2914013234> ?p ?o ?g. }
- W2914013234 endingPage "976" @default.
- W2914013234 startingPage "965" @default.
- W2914013234 abstract "The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth. We hypothesized that mTOR is influential in the intervertebral disc-largest avascular, low-nutrient organ. Our objective was to identify the optimal mTOR inhibitor for treating human degenerative disc disease.mTOR complex 1 (mTORC1) regulates p70/ribosomal S6 kinase (p70/S6K), negatively regulates autophagy, and is controlled by Akt. Akt is controlled by phosphatidylinositol 3-kinase (PI3K) and mTOR complex 2 (mTORC2). mTORC1 inhibitors-rapamycin, temsirolimus, everolimus, and curcumin, mTORC1&mTORC2 inhibitor-INK-128, PI3K&mTOR inhibitor-NVP-BEZ235, and Akt inhibitor-MK-2206-were applied to human disc nucleus pulposus (NP) cells. mTOR signaling, autophagy, apoptosis, senescence, and matrix metabolism were evaluated.mTORC1 inhibitors decreased p70/S6K but increased Akt phosphorylation, promoted autophagy with light chain 3 (LC3)-II increases and p62/sequestosome 1 (p62/SQSTM1) decreases, and suppressed pro-inflammatory interleukin-1 beta (IL-1β)-induced apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity (versus rapamycin, 95% confidence interval (CI) -0.431 to -0.194; temsirolimus, 95% CI -0.529 to -0.292; everolimus, 95% CI -0.477 to -0.241; curcumin, 95% CI -0.248 to -0.011) and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage, senescent senescence-associated beta-galactosidase (SA-β-gal) positivity (versus rapamycin, 95% CI -0.437 to -0.230; temsirolimus, 95% CI -0.534 to -0.327; everolimus, 95% CI -0.485 to -0.278; curcumin, 95% CI -0.210 to -0.003) and p16/INK4A expression, and catabolic matrix metalloproteinase (MMP) release and activation. Meanwhile, dual mTOR inhibitors decreased p70/S6K and Akt phosphorylation without enhanced autophagy and suppressed apoptosis, senescence, and matrix catabolism. MK-2206 counteracted protective effects of temsirolimus. Additional disc-tissue analysis found relevance of mTOR signaling to degeneration grades.mTORC1 inhibitors-notably temsirolimus with an improved water solubility-but not dual mTOR inhibitors protect against inflammation-induced apoptosis, senescence, and matrix catabolism in human disc cells, which depends on Akt and autophagy induction." @default.
- W2914013234 created "2019-02-21" @default.
- W2914013234 creator A5009632638 @default.
- W2914013234 creator A5019017816 @default.
- W2914013234 creator A5019082203 @default.
- W2914013234 creator A5035062633 @default.
- W2914013234 creator A5039950300 @default.
- W2914013234 creator A5052598846 @default.
- W2914013234 creator A5059595447 @default.
- W2914013234 creator A5060259193 @default.
- W2914013234 creator A5062506663 @default.
- W2914013234 creator A5069864719 @default.
- W2914013234 date "2019-06-01" @default.
- W2914013234 modified "2023-10-16" @default.
- W2914013234 title "Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction" @default.
- W2914013234 cites W1599948062 @default.
- W2914013234 cites W1817479092 @default.
- W2914013234 cites W1966082815 @default.
- W2914013234 cites W1966188170 @default.
- W2914013234 cites W1967695858 @default.
- W2914013234 cites W1969157667 @default.
- W2914013234 cites W1984621921 @default.
- W2914013234 cites W2006806309 @default.
- W2914013234 cites W2007413067 @default.
- W2914013234 cites W2009007518 @default.
- W2914013234 cites W2014892893 @default.
- W2914013234 cites W2016091891 @default.
- W2914013234 cites W2021449823 @default.
- W2914013234 cites W2022572059 @default.
- W2914013234 cites W2024585159 @default.
- W2914013234 cites W2036781838 @default.
- W2914013234 cites W2041141449 @default.
- W2914013234 cites W2042141743 @default.
- W2914013234 cites W2042814728 @default.
- W2914013234 cites W2048376025 @default.
- W2914013234 cites W2061401525 @default.
- W2914013234 cites W2070417694 @default.
- W2914013234 cites W2073429636 @default.
- W2914013234 cites W2076388773 @default.
- W2914013234 cites W2092798278 @default.
- W2914013234 cites W2104908670 @default.
- W2914013234 cites W2105081732 @default.
- W2914013234 cites W2106755981 @default.
- W2914013234 cites W2107277218 @default.
- W2914013234 cites W2109034822 @default.
- W2914013234 cites W2112458458 @default.
- W2914013234 cites W2113317783 @default.
- W2914013234 cites W2116271681 @default.
- W2914013234 cites W2119683782 @default.
- W2914013234 cites W2123487526 @default.
- W2914013234 cites W2126783165 @default.
- W2914013234 cites W2128431867 @default.
- W2914013234 cites W2137173580 @default.
- W2914013234 cites W2138302361 @default.
- W2914013234 cites W2141424872 @default.
- W2914013234 cites W2151819466 @default.
- W2914013234 cites W2153607816 @default.
- W2914013234 cites W2159750196 @default.
- W2914013234 cites W2169128609 @default.
- W2914013234 cites W2319357123 @default.
- W2914013234 cites W2561417850 @default.
- W2914013234 cites W2751831991 @default.
- W2914013234 cites W2752326209 @default.
- W2914013234 cites W4293765706 @default.
- W2914013234 cites W4361868163 @default.
- W2914013234 doi "https://doi.org/10.1016/j.joca.2019.01.009" @default.
- W2914013234 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30716534" @default.
- W2914013234 hasPublicationYear "2019" @default.
- W2914013234 type Work @default.
- W2914013234 sameAs 2914013234 @default.
- W2914013234 citedByCount "47" @default.
- W2914013234 countsByYear W29140132342019 @default.
- W2914013234 countsByYear W29140132342020 @default.
- W2914013234 countsByYear W29140132342021 @default.
- W2914013234 countsByYear W29140132342022 @default.
- W2914013234 countsByYear W29140132342023 @default.
- W2914013234 crossrefType "journal-article" @default.
- W2914013234 hasAuthorship W2914013234A5009632638 @default.
- W2914013234 hasAuthorship W2914013234A5019017816 @default.
- W2914013234 hasAuthorship W2914013234A5019082203 @default.
- W2914013234 hasAuthorship W2914013234A5035062633 @default.
- W2914013234 hasAuthorship W2914013234A5039950300 @default.
- W2914013234 hasAuthorship W2914013234A5052598846 @default.
- W2914013234 hasAuthorship W2914013234A5059595447 @default.
- W2914013234 hasAuthorship W2914013234A5060259193 @default.
- W2914013234 hasAuthorship W2914013234A5062506663 @default.
- W2914013234 hasAuthorship W2914013234A5069864719 @default.
- W2914013234 hasBestOaLocation W29140132341 @default.
- W2914013234 hasConcept C104202773 @default.
- W2914013234 hasConcept C107846503 @default.
- W2914013234 hasConcept C126322002 @default.
- W2914013234 hasConcept C185592680 @default.
- W2914013234 hasConcept C190283241 @default.
- W2914013234 hasConcept C203522944 @default.
- W2914013234 hasConcept C2777949483 @default.
- W2914013234 hasConcept C2779699572 @default.
- W2914013234 hasConcept C2908656506 @default.
- W2914013234 hasConcept C43060935 @default.