Luteolin Limits Infarct Size and Improves Cardiac Function after Myocardium Ischemia/Reperfusion Injury in Diabetic Rats

Sun, Dongdong; Huang, Jie; Zhang, Zheng; Gao, Haokao; Li, Jiayi; Shen, Min; Cao, Feng; Wang, Haichang

doi:10.1371/journal.pone.0033491

Cited by 103 publications

(77 citation statements)

References 31 publications

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“…2C). The resultant viability loss was accompanied by decreased phosphorylation of proteins targeted by RSKs, such as BAD (21,22), which is a proapoptotic protein (Fig. 2D).…”

Section: Effect Of Luteolin On Viability Chemosensitivity and Apoptomentioning

confidence: 99%

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells

Deng

Jiang

et al. 2017

Oncology Letters

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Abstract. Ribosomal S6 kinases (RSKs) are directly regulated by extracellular signal-regulated kinase (ERK) signaling and are implicated in cell growth, survival, motility and senescence. The present study observed that RSK1 was overexpressed in primary untreated leukemia patient bone marrow samples compared with the expression at the complete remission stage, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a high RSK1 expression (relative expression ≥10) was associated with a significantly shorter overall survival (P=0.038) compared with that in patients with low RSK1 expression (relative expression <10). The current study also investigated the effect of luteolin, a novel p90 ribosomal S6 kinase (RSK) inhibitor extracted from Reseda odorata L., which shows strong biochemical functions including anti-allergy, anti-inflammation and anti-cancer functions, in MOLM-13 and Kasumi-1 leukemic cells. The cell viability, apoptosis and migration ability analysis were assessed by performing a cell counting kit-8 assay, Annexin V-FITC/PI double staining and migration filter assay, respectively. The results indicated that luteolin inhibited the growth of the leukemic cell lines through induction of apoptosis, while the migration ability was also suppressed. Overexpression of RSK1 by plasmid transfection was found to decrease the luteolin-induced apoptosis and migration capabilities. By contrast, knockdown of the RSK1 expression by small interfering RNA appeared to induce the same effect as luteolin on MOLM-13 and Kasumi-1 leukemic cells. In conclusion, these results suggest that luteolin inhibits leukemic cell proliferation and induces apoptosis by inhibition of the RSK1 pathways. IntroductionRibosomal S6 kinases (RSKs) are a family of serine/threonine protein kinases that are directly regulated by extracellular signal-regulated kinase (ERK) signaling. RSK1, a member of the RSK family, was initially identified as an X-linked gene in patients with mental retardation (1-3). Typically, RSK is expressed in the cerebellum during embryogenesis and silenced postnatally. Aberrant RSK signaling is integral for various types of cancer, including breast, colon and renal cancer, as well as melanoma. Li et al (4) observed that the p90 RSK2-cAMP response element-binding protein (CREB) pathway is commonly activated in diverse metastatic human cancer cells. Degen et al (5) also demonstrated this phenomenon, and further observed that overexpression of RSK3 and RSK1 supports cellular proliferation under the PI3K signaling pathway blockade. This occurs through the inhibition of apoptosis and regulation of cellular translation in squamous carcinoma cell through phosphorylation of RSK and eukaryotic translation initiation factor 4B. It is thus reported that RSK1 serves a role in squamous carcinoma cell growth and proliferation. In addition, Cohen et al (6) observed that RSK1 overexpression is associated with sunitinib resistance in renal cell carcinoma cell lines. Elf et al (7) also reported that, altho...

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“…2C). The resultant viability loss was accompanied by decreased phosphorylation of proteins targeted by RSKs, such as BAD (21,22), which is a proapoptotic protein (Fig. 2D).…”

Section: Effect Of Luteolin On Viability Chemosensitivity and Apoptomentioning

confidence: 99%

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells

Deng

Jiang

et al. 2017

Oncology Letters

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“…After protein concentration, quantization was performed with the modified Bradford assay (Bio-Rad Laboratories, Hercules, CA, USA) 19 and 40 mg total protein was subsequently used for Western blotting with primary antibodies against PHB1, PHB2, angiotensin I and II (Santa Cruz Biotechnology, Inc., Dallas, TX, USA), ACE1, ACE2, TGF-β1, collagen IV (Col-IV), and fibronectin (FN); all from Abcam (Cambridge, MA, USA) unless stated otherwise. Beta-actin was used as an internal loading control.…”

Section: Western Blot Analysismentioning

confidence: 99%

Effect of all-trans retinoic acid treatment on prohibitin and renin–angiotensin–aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury

Zhou

Liang

et al. 2014

J Renin Angiotensin Aldosterone Syst

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Background and objective: All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensinaldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. Methods: The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/ reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Results: Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS,; each p < 0.05), but positively correlated with ACE2, SOD, and GSH (PHB1: r = 0.796, 0.879, 0.824; PHB2: r = 0.785, 0.914, 0.849; each p < 0.05). ACE1 was positively correlated with angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and negatively correlated with ACE2, SOD, and GSH (each p < 0.05). ACE2 was negatively correlated with ACE1, angiotensin I, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA, and positively correlated with SOD and GSH (each p < 0.05). Conclusion:The results suggest that ATRA acts as a positive regulator of PHB1, PHB2 and ACE2, and as a negative regulator of ACE1, angiotensin I, and angiotensin II in a RTEC model system under hypoxia/reoxygenation conditions.

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“…Leakage of these cytosolic enzymes indicates myocardial damage. Many studies have shown that myocardial I/R injury increased the release of LDH [31] and CK-MB in diabetic rats [32,33].…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective Role of Saxagliptin through Antioxidant Mechanism in Experimental Myocardial Infarction in STZ Induced Diabetic Rats

Vkk¹,

Akula²

2017

Clin Exp Pharmacol

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Saxagliptin (Dpp-4 inhibitor) is a newer anti-diabetic drug for type 2 diabetes mellitus. It has beneficial effect on glycemic control and weight neutral but its effects on the heart during ischemic reperfusion periods are not known. We investigated the effect of Saxagliptin on infarct size in a clinically relevant cardiac I/R injury model in type 2 diabetic rats and its underlying cardioprotective effects. Normal and diabetic rats were randomized to receive Saxagliptin 5 mg/kg b.wt. orally for a period of 4 weeks and were subjected to 30 min left anterior descending artery coronary artery occlusion followed by 4 h of reperfusion. Percentage left ventricle infarction, cardiac biomarkers (SGOT, CK, CKMB) oxidative stress markers (malondialdehyde, catalase, SOD) were analysed. When compared to control group, saxagliptin produced significant dose-dependent reduction in percentage infarct volume. Saxagliptin, at 5 mg/kg b.wt. dose, there was a significant reduction in SGOT, CK CKMB and MDA levels and in contrast there was a significant increase in anti-oxidant enzymes such as SOD and catalase levels. Saxagliptin decreases infarct size and showed significant cardioprotective action mediated by antioxidant mechanisms.

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Luteolin Limits Infarct Size and Improves Cardiac Function after Myocardium Ischemia/Reperfusion Injury in Diabetic Rats

Cited by 103 publications

References 31 publications

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells

Luteolin, a novel p90 ribosomal S6 kinase inhibitor, suppresses proliferation and migration in leukemia cells

Effect of all-trans retinoic acid treatment on prohibitin and renin–angiotensin–aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury

Cardioprotective Role of Saxagliptin through Antioxidant Mechanism in Experimental Myocardial Infarction in STZ Induced Diabetic Rats

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