Interleukin 6 protects H<sub>2</sub>O<sub>2</sub>‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation

Jia, Yuhua; Zhou, Fenghua; Deng, Peng; Fan, Qin; Li, Chunhua; Liu, Yawei; Fu, Xiu‐Qiong; Zhou, Yingchun; Xu, Xijin; Sun, Xuegang

doi:10.1002/cbf.2820

Cited by 16 publications

(8 citation statements)

References 26 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To further explore the involved molecules in apigenin-induced apoptosis in OxLDL-loaded MPMs, two-dimensional electrophoresis (2-DE) and mass spectrometry were performed as described previously [ 23 ]. Twenty-eight proteins were identified successfully including fourteen downregulated spots and fourteen upregulated spots caused by OxLDL ( Figure 3(a) ).…”

Section: Resultsmentioning

confidence: 99%

Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Zeng

Liu

Wang

et al. 2015

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Macrophage survival is believed to be a contributing factor in the development of early atherosclerotic lesions. Dysregulated apoptosis of macrophages is involved in the inflammatory process of atherogenesis. Apigenin is a flavonoid that possesses various clinically relevant properties such as anti-inflammatory, antiplatelet, and antitumor activities. Here we showed that apigenin attenuated atherogenesis in apoE −/− mice in an in vivo test. In vitro experiments suggested that apigenin induced apoptosis of oxidized low density lipoprotein- (OxLDL-) loaded murine peritoneal macrophages (MPMs). Proteomic analysis showed that apigenin reduced the expression of plasminogen activator inhibitor 2 (PAI-2). PAI-2 has antiapoptotic effects in OxLDL-loaded MPMs. Enhancing PAI-2 expression significantly reduced the proapoptosis effects of apigenin. Molecular docking assay with AutoDock software predicted that residue Ser473 of Akt1 is a potential binding site for apigenin. Lentiviral-mediated overexpression of Akt1 wild type weakened the proapoptosis effect of apigenin in OxLDL-loaded MPMs. Collectively, apigenin executes its anti-atherogenic effects through inducing OxLDL-loaded MPMs apoptosis. The proapoptotic effects of apigenin were at least partly attributed to downregulation of PAI-2 through suppressing phosphorylation of AKT at Ser473.

show abstract

Section: Resultsmentioning

confidence: 99%

Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Zeng

Liu

Wang

et al. 2015

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

show abstract

“…A recent study suggests that IL-6 provides protection against colitis via a mechanism dependent on Stat3 activation in the intestinal epithelium [56]. We and others have shown that IL-6 increases expression of PHB through Stat3 transcriptional activation to promote survival of IECs, cardiomyocytes, and hepatocytes [53-55, 57]. IL-6 protective effects in cardiomyocytes are dependent upon IL-6 induction of PHB [58] and phosphorylation of mitochondrial S727-Stat3 [59].…”

Section: Discussionmentioning

confidence: 99%

Prohibitin 1 modulates mitochondrial function of Stat3

Han

Souza

et al. 2014

Cellular Signalling

View full text Add to dashboard Cite

Mitochondrial dysfunction in intestinal epithelial cells (IEC) is thought to precede the onset of inflammatory bowel diseases (IBD). Expression of Prohibitin 1 (PHB), a mitochondrial protein required for optimal electron transport chain (ETC) activity, is decreased in mucosal biopsies during active and inactive IBD. In addition to its activities as a transcription factor, Signal Transducer and Activator of Transcription 3 (Stat3) resides in the mitochondria of cells where phosphorylation at S727 is required for optimal ETC activity and protects against stress-induced mitochondrial dysfunction. Here, we show that PHB overexpression protects against mitochondrial stress and apoptosis of cultured IECs induced by TNFα, which is a pro-inflammatory cytokine involved in IBD pathogenesis. Expression of pS727-Stat3 dominant negative eliminates protection by PHB against TNFα-induced mitochondrial stress and apoptosis. PHB interacts with pS727-Stat3 in the mitochondria of cultured IECs and in colonic epithelium from wild-type mice. Our data suggest a protective role of PHB that is dependent on pS727-Stat3 to prevent mitochondrial dysfunction in IECs. Reduced levels of PHB during IBD may be an underlying factor promoting mitochondrial dysfunction of the intestinal epithelium.

show abstract

“…Hydrogen peroxide (H 2 O 2 ) is a potent reactive oxygen species that causes mitochondrial dysfunction and cell death. Preconditioning cells with IL-6 decreases H 2 O 2 -induced cell death by increasing the expression of prohibitin, which is involved in mitochondrial biogenesis and metabolism, apoptosis and replicative senescence [137]. In addition to signalling through STAT-3, the stress-induced activation catalase.…”

Section: Maintenance Of Redox Potentialmentioning

confidence: 99%

Role of interleukin-6 in cancer progression and therapeutic resistance

et al. 2016

View full text Add to dashboard Cite

In the last several decades, the number of people dying from cancer-related deaths has not reduced significantly despite phenomenal advances in the technologies related to diagnosis and therapeutic modalities. The principal cause behind limitations in the curability of this disease is the reducing sensitivity of the cancer cells towards conventional anticancer therapeutic modalities, particularly in advance stages of the disease. Amongst several reasons, certain secretory factors released by the tumour cells into the microenvironment have been found to confer resistance towards chemo- and radiotherapy, besides promoting growth. Interleukin-6 (IL-6), one of the major cytokines in the tumour microenvironment, is an important factor which is found at high concentrations and known to be deregulated in cancer. Its overexpression has been reported in almost all types of tumours. The strong association between inflammation and cancer is reflected by the high IL-6 levels in the tumour microenvironment, where it promotes tumorigenesis by regulating all hallmarks of cancer and multiple signalling pathways, including apoptosis, survival, proliferation, angiogenesis, invasiveness and metastasis, and, most importantly, the metabolism. Moreover, IL-6 protects the cancer cells from therapy-induced DNA damage, oxidative stress and apoptosis by facilitating the repair and induction of countersignalling (antioxidant and anti-apoptotic/pro-survival) pathways. Therefore, blocking IL-6 or inhibiting its associated signalling independently or in combination with conventional anticancer therapies could be a potential therapeutic strategy for the treatment of cancers with IL-6-dominated signalling.

show abstract

Interleukin 6 protects H₂O₂‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation

Abstract: Our results provide direct evidence that prohibitin is a protective factor of IL-6 preconditioning in H(2)O(2)-induced neonatal rat ventricular cardiomyocytes death. The upregulation of prohibitin by IL-6 is, at least, partially regulated through STAT3 phosphorylation.

Cited by 16 publications

References 26 publications

Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Prohibitin 1 modulates mitochondrial function of Stat3

Role of interleukin-6 in cancer progression and therapeutic resistance

Contact Info

Product

Resources

About

Interleukin 6 protects H2O2‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation

Abstract: Our results provide direct evidence that prohibitin is a protective factor of IL-6 preconditioning in H(2)O(2)-induced neonatal rat ventricular cardiomyocytes death. The upregulation of prohibitin by IL-6 is, at least, partially regulated through STAT3 phosphorylation.

Cited by 16 publications

References 26 publications

Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2

Prohibitin 1 modulates mitochondrial function of Stat3

Role of interleukin-6 in cancer progression and therapeutic resistance

Contact Info

Product

Resources

About

Interleukin 6 protects H₂O₂‐induced cardiomyocytes injury through upregulation of prohibitin via STAT3 phosphorylation