Essential Role of Angiotensin Receptors in the Modulation of Intestinal Epithelial Cell Apoptosis

Wang, Wensheng; Sun, Lihua; Xiao, Weidong; Yang, Hua

doi:10.1097/mpg.0b013e31829f1336

Cited by 12 publications

(20 citation statements)

References 33 publications

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“…Numerous regulatory molecules control this process, which mediated by apoptotic signaling. The ratio of Bcl-2/Bax protein determines cell survival or death after I/R [23,24]. The cleavage of caspase-3 is the final step of the process that initiates the apoptotic signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

Zhou

Che

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ischemia-reperfusion (I/R) adversely affects the intestinal mucosa. The major mechanisms of I/R are the generation of reactive oxygen species (ROS) and apoptosis. Salvianolic acid A (SalA) is suggested to be an effective antioxidative and antiapoptotic agent in numerous pathological injuries. The present study investigated the protective role of SalA in I/R of the intestine. Methods: Adult male Sprague-Dawley rats were subjected to intestinal I/R injury in vivo. In vitro experiments were performed in IEC-6 cells subjected to hypoxia/ reoxygenation (H/R) stimulation to simulate intestinal I/R. TNF-α, IL-1β, and IL-6 levels were measured using enzyme-linked immunosorbent assay. Malondialdehyde and myeloperoxidase and glutathione peroxidase levels were measured using biochemical analysis. Apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining or flow cytometry in vivo and in vitro. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. Western blotting was performed to determine the expression of heme oxygenase-1 (HO-1), Nrf2 and proteins associated with apoptosis. The mRNA expressions of Nrf2 and HO-1 were detected by quantitative real-time polymerase chain reaction in vivo and in vitro. Results: Malondialdehyde level and myeloperoxidase and glutathione peroxidase, TNF-α, IL-1β, and IL-6 levels group in intestinal tissue decreased significantly in the SalA pretreatment groups compared to the I/R group. SalA markedly abolished intestinal injury compared to the I/R group. SalA significantly attenuated apoptosis and increased Nrf2/HO-1 expression in vivo and in vitro. However, Nrf2 siRNA treatment partially abrogated the above mentioned effects of SalA in H/R-induced ROS and apoptosis in IEC-6 cells. Conclusion: The present study demonstrated that SalA ameliorated oxidation, inhibited the release of pro-inflammatory cytokines and alleviated apoptosis in I/R-induced injury and that these protective effects may partially occur via regulation of the Nrf2/ HO-1 pathways.

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Section: Discussionmentioning

confidence: 99%

Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

Zhou

Che

et al. 2018

Cell Physiol Biochem

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“…Angiotensin II has previously been demonstrated to induce apoptosis via AT1R in myocytes and IECs, and the underlying mechanism may be partially due to its regulatory effect on the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) pathway ( 10 , 11 ). Bax and Bcl-2 are important proapoptotic and anti-apoptotic mediators, respectively, which have a crucial role in regulating IEC apoptosis via the intrinsic apoptotic pathway ( 12 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease

Liu

Shi

Wang

et al. 2015

Molecular Medicine Reports

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Angiotensin II, which is the main effector of the renin-angiotensin system, has an important role in intestinal inflammation via the angiotensin II type 1 receptor (AT1R). The present study aimed to investigate the protective effects of the AT1R blocker losartan on 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis. Losartan was administered to male adult C57BL/6 J mice 2 weeks prior to the induction of colitis, and images of the whole colon were captured to record changes, scored according to a microscopic scoring system, and reverse transcription-quantitative polymerase chain reaction were performed in order to investigate colonic inflammation. In addition, intestinal epithelial barrier permeability was evaluated, and intestinal epithelial cell (IEC) apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and apoptosis-related protein expression levels were detected by western blotting. Losartan was able to attenuate TNBS-induced body weight loss and colonic damage. Furthermore, T helper 1-mediated proin-flammatory cytokines were suppressed by losartan, and gut permeability was largely preserved. TUNEL staining revealed reduced IEC apoptosis in the losartan-treated mice. Losartan also increased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio and suppressed caspase-3 induction. These results suggested that the AT1R blocker losartan may attenuate TNBS-induced colitis by inhibiting the apoptosis of IECs. The effects of losartan were partially mediated through increasing the Bcl-2/Bax ratio and subsequently suppressing the induction of the proapoptotic mediator caspase-3.

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“…Both experimental animals (168) and humans (169) with acute intestinal inflammation have elevated plasma levels of ACE2 and angiotensin-(1-7). In animal models of acute intestinal inflammation, treatment with ARBs down regulates proinflammatory cytokines and reduces oxidative stress and epithelial apoptosis (170)(171)(172), and statins have similar effects (173)(174)(175). Apoptosis of intestinal epithelial cells is a common finding in human and animal studies of critical illness (164).…”

Section: [Interestingly Influenza Viruses Naturally Cause Gastrointementioning

confidence: 99%

Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola

2016

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There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a "top down" approach to developing specific new drug treatments is unlikely to be effective. However, a "bottom up" approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.

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Essential Role of Angiotensin Receptors in the Modulation of Intestinal Epithelial Cell Apoptosis

Abstract: These findings suggest that ANGII plays an important role in the regulation of apoptosis of the IECs. AT1R may be of crucial importance for the modulation of intestinal EC apoptosis.

Cited by 12 publications

References 33 publications

Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

AT1R blocker losartan attenuates intestinal epithelial cell apoptosis in a mouse model of Crohn's disease

Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola

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