Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats

Esmaeili, Zeinab; Niaz, Qamar; Saffari, Partow Mirzaee; Dehpour, Ahmad Reza; Rezayat, Seyed Mahdi; Jazaeri, Farahnaz

doi:10.1016/j.lfs.2021.119261

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…Moreover, a downregulation of HSP 70 expression occurred in the endoplasmic reticulum pathway during protein processing by 55.32% and 10.43%, respectively, and HSP 70 was the core protein of the PPI network (Figure S9). It was reported that HSP 70 could protect the cells in stress and has antiapoptotic and cytoprotective effects, and the endoplasmic reticulum stress (Figure III) was also reported to be involved in MC-LR toxicity in HepG2 cells . Most importantly, the most widely studied and accepted mechanism of MC-LR toxicity is the inhibition of PP1 .…”

Section: Discussionmentioning

confidence: 99%

Microcystins-Loaded Aged Nanoplastics Provoke a Metabolic Shift in Human Liver Cells

Shen

Salam

et al. 2023

Environ. Sci. Technol.

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Studies concerning the toxicity of pollutant-loaded nanoplastics (NPs) toward humans are still in their infancy. Here, we evaluated the adsorption of microcystins (MCs) by pristine and aged polystyrene nanoplastics (PSNPs), prepared MCs-loaded aged PSNPS (1, 5, 10, 15, and 19 μg/mg), and systematically mapped the key molecular changes induced by aged and MCs-loaded PSNPs to human hepatoblastoma (HepG2) cells. According to the results, MC-LR adsorption is increased 2.64-fold by aging, and PSNP accumulation is detected in HepG2 cells. The cytotoxicity of the MC-LR-loaded aged PSNPs showed a positive relationship with the MC-LR amount, as the cell viability in the 19 μg/mg loading treatment (aPS-MC19) was 10.84% lower than aged PSNPs; meanwhile, more severe oxidative damage was observed. Primary approaches involved stressing the endoplasmic reticulum and reducing protein synthesis that the aged PSNPs posed for HepG2 cells, while the aggravated cytotoxicity in aPS-MC19 treatment was a combined result of the metabolic energy disorder, oxidative damage, endoplasmic reticulum stress, and downregulation of the MC-LR target protein. Our results confirm that the aged PSNPs could bring more MC-LR into the HepG2 cells, significantly interfere with biological processes, and provide new insight into deciphering the risk of NPs to humans.

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Section: Discussionmentioning

confidence: 99%

Microcystins-Loaded Aged Nanoplastics Provoke a Metabolic Shift in Human Liver Cells

Shen

Salam

et al. 2023

Environ. Sci. Technol.

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“…Upon exposure to various stimuli such as cellular stress and chemical damage, cells upregulate the expression of HSP70 to prevent protein aggregation [ 49 ]. Notably, research has revealed that HSP70 has a negative impact on epithelial–mesenchymal transition (EMT), a key process involved in fibrosis [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TβRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations

Mohammed,

Abdel-Reheim,

Alamri

et al. 2023

Pharmaceuticals

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Liver fibrosis is a progressive condition characterized by the build-up of fibrous tissue resulting from long-term liver injury. Although there have been advancements in research and treatment, there is still a need for effective antifibrotic medication. HSP90 plays a crucial role in the development of fibrosis. It acts as a molecular chaperone that assists in the proper folding and stability of TβRII, potentially regulating the signaling of TGF-β1. It has been established that TβRII can be degraded through the proteasome degradation system, either via ubiquitination-dependent or -independent pathways. In the present study, STA9090 demonstrated promising effects in both in vitro and in vivo models. It reduced LDH leakage, prolonged the survival rate of hepatocytes in rats with liver fibrosis, and improved liver function. Importantly, STA9090 exerted pleiotropic effects by targeting proteins involved in limiting collagen production, which resulted in improved microscopic features of the rat livers. Our findings suggest that STA9090-induced inhibition of HSP90 leads to the degradation of TβRII, a fibrogenic client protein of HSP90, through the activation of the 20S proteasomal degradation system. We also revealed that this degradation mechanism is not dependent on the autophagy–lysosomal pathway. Additionally, STA9090 was found to destabilize HIF-1α and facilitate its degradation, leading to the reduced transcription of VEGF. Moreover, STA9090’s ability to deactivate the NFκB signaling pathway highlights its potential as an anti-inflammatory and antifibrotic agent. However, further research is necessary to fully elucidate the underlying mechanisms and fully capitalize on the therapeutic benefits of targeting HSP90 and associated pathways.

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“…No. MBS764880, MyBioSource, Inc., San Diego, USA" [14,15], Rat TNF-α ELISA kit of a 96-well plate "Cat. No.…”

Section: Serum Bnp Atl Ast and Heart Tnf-α And Nrf2 Levelsmentioning

confidence: 99%

Effects of Gap 26, a Connexin 43 Inhibitor, on Cirrhotic Cardiomyopathy in Rats

Mohammed,

Tavangar,

Khodadoostan

et al. 2024

Cureus

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IntroductionCirrhotic cardiomyopathy (CCM) is recognized by impaired cardiac responsiveness to stress, prolonged QT interval, and systolic and diastolic dysfunctions. Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Connexin 43 (Cx43) inhibition showed cardio-protective effects. Peptide drug Cx43 inhibitor, Gap 26, could inhibit gap junction 43. This study was designed to evaluate the effects of a connexin mimetic peptide, Gap 26, in the CCM model in rats. MethodsThe cirrhosis was induced through carbon tetrachloride (CCl4). On day 56, electrocardiography (ECG) was recorded, spleen weight was measured, and tissue and serum samples were collected. Further, Cx43 mRNA expression in heart tissue was checked. ResultsThe chronotropic responses decreased in the CCl4/saline and increased in the CCl4/Gap. The spleen weight, QTc interval, and brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), aspartate aminotransferase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels elevated in the CCl4/saline, and the spleen weight, QTc interval, and MDA and ALT levels were reduced by Gap 26 treatment. The level of nuclear factor (erythroid-derived 2) factor 2 (Nrf2) decreased in the CCl4/saline. The Cx43 expression was downregulated in the CCl4/saline and upregulated with the Gap 26 treatment. ConclusionGap 26 not only alleviated the chronotropic hyporesponsiveness and the severity of liver damage and upregulated the atrial Cx43 expression, but it also had an antioxidant effect on the heart.

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Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats

Cited by 11 publications

References 48 publications

Microcystins-Loaded Aged Nanoplastics Provoke a Metabolic Shift in Human Liver Cells

Microcystins-Loaded Aged Nanoplastics Provoke a Metabolic Shift in Human Liver Cells

STA9090 as a Potential Therapeutic Agent for Liver Fibrosis by Modulating the HSP90/TβRII/Proteasome Interplay: Novel Insights from In Vitro and In Vivo Investigations

Effects of Gap 26, a Connexin 43 Inhibitor, on Cirrhotic Cardiomyopathy in Rats

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