NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin α1 β1

2011 ◽  
Vol 79 (8) ◽  
pp. 2530-2542 ◽  
Author(s):  
Rodrigo J. Carbajo ◽  
Libia Sanz ◽  
Silvia Mosulén ◽  
Alicia Pérez ◽  
Cezary Marcinkiewicz ◽  
...  
2021 ◽  
Vol 8 ◽  
Author(s):  
Penglong Wu ◽  
Mingqi Cai ◽  
Jinbao Liu ◽  
Xuejun Wang

Background: Catecholamine surges and resultant excessive β-adrenergic stimulation occur in a broad spectrum of diseases. Excessive β-adrenergic stimulation causes cardiomyocyte necrosis, but the underlying mechanism remains obscure. Necroptosis, a major form of regulated necrosis mediated by RIPK3-centered pathways, is implicated in heart failure; however, it remains unknown whether excessive β-adrenergic stimulation-induced cardiac injury involves necroptosis. Hence, we conducted the present study to address these critical gaps.Methods and Results: Two consecutive daily injections of isoproterenol (ISO; 85 mg/kg, s.c.) or saline were administered to adult mixed-sex mice. At 24 h after the second ISO injection, cardiac area with Evans blue dye (EBD) uptake and myocardial protein levels of CD45, RIPK1, Ser166-phosphorylated RIPK1, RIPK3, and Ser345-phosphorylated MLKL (p-MLKL) were significantly greater, while Ser321-phosphorylated RIPK1 was significantly lower, in the ISO-treated than in saline-treated wild-type (WT) mice. The ISO-induced increase of EBD uptake was markedly less in RIPK3−/− mice compared with WT mice (p = 0.016). Pretreatment with the RIPK1-selective inhibitor necrostatin-1 diminished ISO-induced increases in RIPK3 and p-MLKL in WT mice and significantly attenuated ISO-induced increases of EBD uptake in WT but not RIPK3−/− mice.Conclusions: A large proportion of cardiomyocyte necrosis induced by excessive β-adrenergic stimulation belongs to necroptosis and is mediated by a RIPK1–RIPK3-dependent pathway, identifying RIPK1 and RIPK3 as potential therapeutic targets for catecholamine surges.


Structure ◽  
2020 ◽  
Author(s):  
Shu Zhou ◽  
Pontus Pettersson ◽  
Jingjing Huang ◽  
Peter Brzezinski ◽  
Régis Pomès ◽  
...  

RNA ◽  
2002 ◽  
Vol 8 (1) ◽  
pp. 83-96 ◽  
Author(s):  
ERIC S. DEJONG ◽  
WILLIAM F. MARZLUFF ◽  
EDWARD P. NIKONOWICZ

Biochemistry ◽  
1997 ◽  
Vol 36 (37) ◽  
pp. 11188-11197 ◽  
Author(s):  
Helena Berglund ◽  
Magnus Wolf-Watz ◽  
Thomas Lundbäck ◽  
Susanne van den Berg ◽  
Torleif Härd

2002 ◽  
Vol 277 (32) ◽  
pp. 29172-29180 ◽  
Author(s):  
Vincent Raussens ◽  
Carolyn M. Slupsky ◽  
Robert O. Ryan ◽  
Brian D. Sykes

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