IndraLab

Statements



sparser
"Alternatively, ROS could interact with a conserved thiol pair of Hsp90 rendering it nonfunctional, thereby interfering with chaperone binding to hERG."

sparser
"Effect of ALLN on the binding of HERG protein and molecular chaperone CNX/CRT in each cell model."

sparser
"To determine the role of chaperone CNX/CRT in the process of ALLN to correct the translocation of HERG-A561V mutant protein, the binding of HERG protein and molecular chaperone CNX/CRT in the HERG-WT, HERG- A561V, HERG-L539fs/47, HERG-WT/A561V, HERG-WT/L539fs/47 cell models were detected by immunoprecipitation after 24-h treatment with or without ALLN (10 μmol/l)."

sparser
"Arsenic trioxide was shown to reduce the formation of hERGchaperone (Hsp90 and Hsp70) complexes, resulting in disruption of hERG trafficking ( Ficker et al., 2004 )."

sparser
"Effect of Prop on the binding of HERG protein and molecular chaperone CNX/CRT in each cell model."

sparser
"To determine if CH prolonged the association of hERG with Hsp90 chaperone, we treated cells with geldanamycin, a specific inhibitor of Hsp90 binding and analyzed hERG expression."

sparser
"Many chaperone molecules, such as Hsp70/Hsc70, Hsp90 or FK506-binding protein (FKBP38), interact with HERG to facilitate its proper folding [10] ."

sparser
"Arsenic trioxide was the first example of a therapeutic drug that caused QT prolongation, TdP, and sudden death by reducing the formation of the hERG-chaperone complexes Hsp 70 and Hsp 90 ( xref ; xref )."

sparser
"Further investigation is necessary to determine each of the chaperones that interact with HERG and if the chaperone-HERG interactions are regulated by increased cAMP or PKA activation."

sparser
"We therefore turned to exploring whether THIO prevents maturation of hERG channels via inhibiting chaperone-hERG interactions; to this end, we performed coimmunoprecipitation experiments to determine the association of hERG protein with Hsp70."

sparser
"For example Ficker et al. [113] demonstrated that arsenic trioxide (“antineoplastic” or “cytotoxic” molecule) did not show any direct inhibitory effect on hERG channel activity but disrupted the hERG [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Pharmacological chaperones may serve to disrupt the interaction of immature Kv11.1 proteins with ER chaperone and quality-control proteins including Hsp40 (40-kDa heat shock protein), Hsc70 (70-kDa heat shock cognate protein), Hsp90 (90-kDa heat shock protein), FLBP38, calnexin, and numerous other chaperones, thereby protecting mutant proteins from degradation and alternatively by attenuating digestion by enzymes such as trypsin xref – xref ."

sparser
"Co-immunoprecipitation experiments revealed that hypoxia inhibited interaction of hERG with Hsp90 chaperone required for maturation, which was restored in the presence of ROS scavengers."

sparser
"Arsenic trioxide (As 2 O 3 ) is the first example of a drug that produces hERG channel liability through the inhibition of channel protein trafficking by disrupting hERG-chaperone complexes to reveal a new significant mechanism in decreased I Kr current ( xref )."

sparser
"This is now proposed to occur by two mechanisms: a fast process that increases cardiac calcium currents and a longer-term process that reduces hERG expression at the cell membrane, by inhibiting hERG-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"This could result in a conformational change resulting in misfolding and altered hERG-chaperone interactions."

sparser
"This includes the use computational modelling to study the implications of hERG mutations on hERG structure and trafficking, the interactions of hERG with hERG chaperone proteins and with membrane-soluble molecules, the mechanisms of drugs that inhibit hERG trafficking and drugs that rescue hERG mutations."