Arsenic trioxide (As2O3) is used to treat acute promyelocytic leukemia. However, the cardiotoxicity of long QT syndrome restricts its clinical application. Previous studies showed that As2O3 can damage the human ether-a-go-go-related gene (hERG) current via disturbing its trafficking to cellular membrane. This study aimed to investigate whether the As2O3-insulted hERG channel can be rescued by resveratrol, a recognized cardioprotective agent. The whole-cell patch clamp technique was used to record the hERG current and action potential duration. Co-immunoprecipitation and Western blot assay were applied to determine the function of hERG-Hsp70/Hsp90 chaperone complexes and the expression alteration of protein-folding-related proteins, respectively. Compared with treatment of As2O3 alone, co-treatment with resveratrol successfully restored the current and surface expression of hERG and obviously shortened action potential duration in guinea pig ventricular myocytes. Further experiments demonstrate that resveratrol relieved As2O3-caused endoplasmic reticulum (ER) stress by restoring the function of hERG-Hsp70/Hsp90 chaperone complexes and downregulating the protein expression of ER chaperone proteins (calnexin and calreticulin) and activating transcription factor 6. In conclusion, resveratrol was able to rescue the trafficking deficiency and relieve the ER stress (ERS). Our findings suggest that resveratrol has a potential effect to alleviate the adverse effect of As2O3 on cardiotoxicity.
Source of materialThetitle compound was synthesized by the reaction of Ni(OAc) 2 × 4H 2 O( 0.01 mmol), 3-(4-carboxy-phenoxy)phthalic acid (H 3 L) (0.01 mmol), 2,2'-bipyridine (2,2'-bipy, 0.01 mmol), and NaOH (0.0020 g) in the molar ratio of 1:1:1 in 15 ml water. The reaction wascarried outinasealed Teflon-lined stainless steel autoclave reactorat140°C for3days. Afterthe mixture was cooled to room temperature, blue crystals were collected.
DiscussionThe design and synthesis of metal-organic frameworks (MOFs) have attractedc onsiderablea ttention becauseo ft heir potential applications as functionmaterials as well as their structural diversity and intriguing variety of topologies [1][2][3][4][5][6]. In principle, the most effective approach for the construction of MOFs is to rationally modify the building blocks and to control the assembled motifs for required products via selecting different organic ligands. It is well known that carboxylate ligands play an important role in coordination chemistry, which maya dopt diverse binding modes such as monodentate, chelating, and bridging in the syn-syn, syn-anti,and anti-anti configurations. 3-(4-carboxyphenoxy)phthalic acid (H 3 L), as an O-donor ligand with three coordinating carboxylic groups attached at asymmetrical positions of asemirigid V-shaped centralmolecularframework,has been used to constructMOFs [7]. Thea symmetric unit of the title crystal structure contains one Ni(II) ion, one HL ligand, one 2,2'-bipy ligand, and one coordinated water molecule. The Ni(II)ion is six-coordinated by two nitrogen atomsofone 2,2'-bipy ligand, three oxygen atomsoftwo HL ligands, and one oxygen atom from coordinated water molecule, resulting in adistorted octahedral coordination. The Ni-O and Ni-N bond lengths are in the range of 2.054 (1)
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.