Abstract：
:Heart rhythm disturbances have been widely recognized as major triggers of cardiovascular (CV) mortality in chronic kidney disease (CKD) patients. Connexin 43 (Cx43)-composed gap junctions are essential in cardiomyocyte synchronization and may be involved in the pathological response to uremic toxins. Indoxyl sulfate (IS) is one of the most dominant uremic toxins that contribute to CKD-related cardiovascular diseases. In primary cultures of rat neonatal cardiomyocytes, we demonstrated that IS treatment decreased spontaneous contraction without impairing viability. In addition, there was disruption of gap junction intercellular communication (GJIC) between cardiomyocytes after 30 min of IS stimulation. IS caused time- and dose-dependent Cx43 redistribution, and the patterns of Cx43 immunostaining returned to baseline while IS stimulation was removed. Furthermore, IS exposure downregulated Cx43 protein and mRNA levels. Elevated JNK1 and JNK2 phosphorylation was further identified after IS exposure in both rat cardiomyocytes and H9c2 cells. The above changes as well as GJIC and Cx43 suppression were reversed by pretreatment with a JNK inhibitor (SP600125). Inhibition of p-JNK attenuated IS-mediated downward trends in Cx43 transcription and translation. In cardiac muscle from nephrectomy-induced CKD mice, an alteration in Cx43 level was identified at intercalated discs. Our findings disclosed that JNK activation might participate in the remodeling of gap junction and Cx43 expression by uremic toxin-IS both in vitro and in vivo.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Changchien CY,Sung MH,Chang HH,Tsai WC,Peng YS,Chen Ydoi
10.1016/j.cbi.2020.108979subject
Has Abstractpub_date
2020-03-01 00:00:00pages
108979eissn
0009-2797issn
1872-7786pii
S0009-2797(19)31726-0journal_volume
319pub_type
杂志文章abstract：:4-methylesculetin (4 ME) is a natural antioxidant coumarin with protective effects on the intestinal inflammation, in which oxidative stress plays a key role in its aetiology and pathophysiology. Based on this, we examined the antioxidant molecular mechanisms involved in the intestinal anti-inflammatory activity of th...
journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2006.09.013
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(91)90092-l
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(91)90102-d
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(92)90110-7
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2014.06.026
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(02)00059-5
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(89)90119-1
更新日期：1989-01-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2012.10.008
更新日期：2013-02-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(01)00222-8
更新日期：2001-06-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(76)90095-8
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2005.10.004
更新日期：2005-12-15 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109303
更新日期：2020-12-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2011.09.006
更新日期：2012-01-05 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(96)03698-8
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2019.02.026
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journal_title：Chemico-biological interactions
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doi：10.1016/j.cbi.2008.04.024
更新日期：2008-09-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2004.12.005
更新日期：2005-01-15 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2020.109225
更新日期：2020-10-01 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2009.05.012
更新日期：2009-09-14 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章,meta分析
doi：10.1016/j.cbi.2010.12.020
更新日期：2011-05-30 00:00:00
abstract：:The five 5-nitroimidazole derivatives and the four glyoxylic compounds tested in this paper for their interaction with DNA with and without irradiation had previously been reported to act as radiosensitizers at a cellular level. Our aim was to find if the radiosensitizing activity of these products could be due to the...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/0009-2797(89)90038-0
更新日期：1989-01-01 00:00:00
abstract：:Five mouse anti-human butyrylcholinesterase (BChE) monoclonal antibodies bind tightly to native human BChE with nanomolar dissociation constants. Pairing analysis in the Octet system identified the monoclonal antibodies that bind to overlapping and independent epitopes on human BChE. The nucleotide and amino acid sequ...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.11.011
更新日期：2016-01-05 00:00:00
abstract：:Sulfur mustard is a highly toxic chemical warfare agent with devastating impact on intoxicated tissues. DNA cross-links are probably the most toxic DNA lesions induced in the cell by sulfur mustard. The comet assay is a very sensitive method for measuring DNA damage. In the present study using the A-549 lung cell line...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2015.05.009
更新日期：2015-07-25 00:00:00
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journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(85)80170-8
更新日期：1985-08-01 00:00:00
abstract：:This study evaluated relations between exposure to 1,3-butadiene (BD), styrene (STY) and dimethyldithiocarbamate (DMDTC) and mortality from leukemia among synthetic rubber industry workers. Subjects were 13130 men employed for at least 1 year during 1943-1991 at any of six plants that manufactured synthetic rubber. De...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/s0009-2797(01)00223-x
更新日期：2001-06-01 00:00:00
abstract：:Tumor angiogenesis and PI3K/Akt/mTOR pathway are two major molecular objectives for the treatment and management of breast cancer. Here we first time report the molecular mechanism of a marine sponge alkaloid derivative 4-chloro fascapysin (4-CF) for its anticancer and antiangiogenesis potential. It simultaneously tar...
journal_title：Chemico-biological interactions
pub_type： 杂志文章
doi：10.1016/j.cbi.2017.07.017
更新日期：2017-09-25 00:00:00
