scholarly journals δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

2016 ◽  
Vol 39 (3) ◽  
pp. 1118-1128 ◽  
Author(s):  
Feng Zhi ◽  
Lian Xue ◽  
Naiyuan Shao ◽  
Danni Deng ◽  
Xuezhi Kang ◽  
...  

Background: Hypoxic/ischemic injury to the heart is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ischemic events, and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering miRNA expression in the heart under hypoxic conditions. The present study aimed to test our hypothesis. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O2) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected from TaqMan low-density array (TLDA) data and were further analyzed by quantitative real-time PCR. Results: We found that: 1) hypoxia alters the miRNA expression profiles depending on the hypoxic duration; 2) DOR activation shifts miRNA expression profiles in normoxic conditions and upregulates miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, and miR-338; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression and increases the levels of miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, miR-141, miR-200b, and miR-324-3p. For example, miR-196c-5p decreased by 50% while miR-135a-5p increased 2.9 fold after 10 days under hypoxic conditions. Moreover, DOR activation further strengthened the hypoxia-induced increase of the levels of miR-7a-5p. When DOR was activated using UFP-512, the level of miR-107-3p significantly increased 1 day after the administration of UFP-512, but gradually decreased back to normal under normoxia. Conclusion: Hypoxia significantly modifies the miRNA profile in the heart, which can be mimicked or modified by DOR activation. Defining the targeted pathways that regulate the diverse cellular and molecular functions of miRNAs may provide new insights into potential therapies for hypoxic/ischemic injury of the heart.

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Xiaozhou He ◽  
Yilin Yang ◽  
Feng Zhi ◽  
Meredith L Moore ◽  
Xuezhi Kang ◽  
...  

Cardiovascular dysfunction often causes blood/oxygen insufficiency in the kidney that is very sensitive to changes in oxygen/blood delivery. Indeed, hypoxic/ischemic kidney stress is a frequent problem in clinical settings. There is, however, no promising strategy for prevention and treatment of such injury. Since recent studies suggest that microRNAs are differentially involved in hypoxic/ischemic events and delta-opioid receptor (DOR) activation increases antioxidant capacity and protects against hypoxic/ischemic injury, we asked if DOR activation regulates microRNA expression in the kidney under hypoxic condition. We isolated microRNAs from normoxic and hypoxic rat kidneys and used the paired microRNAs for microarray analysis. Thirty-one microRNAs were selected for quantitative PCR analysis based on the microarray data. Among them, 14 microRNAs were significantly altered in response to prolonged hypoxia for 1, 5 and 10 days, DOR activation with UFP-512 (1 mg/kg/day, ip, at days 0, 4 and 8) or a combination of both. Our novel data show that 1) DOR activation shifts miRNA expression profiles in normoxic conditions; 2) hypoxia differentially alters the miRNA expression profiles depending on hypoxic durations; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression. For example, 10-day hypoxia reduced the level of miR-212 by >70% (p<0.001), while DOR activation could mimic such reduction even in normoxic kidney. In contrast, the same stress increased miR-29a by >100% (p<0.05), which could be attenuated by DOR activation. These results suggest that hypoxia comprehensively modifies the microRNA profile within the kidney, which can be mimicked or modified by DOR activation. Illumination of their targeted pathways, that regulate hypoxia sensitive transcription factors, antioxidant capacity, erythropoietin, Golgi-trafficking regulator, neurexophilin, ubiquitin-mediated degradation, intracellular trafficking, scaffolding, Wnt signaling, solute channels and ion homeostasis, may provide new insights into the potential therapeutics for hypoxic/ischemic injury of the kidney.


2017 ◽  
Vol 44 (6) ◽  
pp. 2296-2309 ◽  
Author(s):  
Feng Zhi ◽  
Naiyuan Shao ◽  
Lian Xue ◽  
Yuan Xu ◽  
Xuezhi Kang ◽  
...  

Background/Aims: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O2) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected according to TaqMan low-density array (TLDA) data and analyzed by quantitative real-time PCR. Results: We found that: 1) 1-day hypoxia caused the upregulation of 9 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-122-5p, miR-128a-3p, miR-135b-5p, miR-145-5p, and miR-181a-5p) and the downregulation of 2 miRNAs (miR-34a-5p and miR-182); 2) 5 and 10-days hypoxia altered the expression of 4 miRNAs (miR-34c-5p, miR-184, miR-107-3p and miR192-5p); 3) DOR activation shifted the expression of 8 miRNAs (miR-122-5p, miR-146a-5p, miR-30e-5p, miR-128a-3p, miR-182, miR-192-5p miR-107-3p and miR-184) in normoxic condition; and 4) DOR activation modified hypoxia-induced changes in 6 miRNAs (miR-142-5p, miR-145-5p, miR-146a-5p, miR-204-5p, miR-34a-5p and miR-192-5p). Conclusion: Hypoxia significantly modifies the miRNA profile in the liver, while DOR activation can modify the hypoxic modification. Therefore, it is potentially possible to alter hypoxic/ischemic pathophysiology in the liver through DOR pharmacotherapy.


2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic &#946;-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in &#946;-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of &#946;-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into &#946;-cells, resulting in enhanced &#946;-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of &#946;-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived &#946;-cells to therapeutically relevant outputs will be discussed as well.


Author(s):  
Michela Bulfoni ◽  
Riccardo Pravisani ◽  
Emiliano Dalla ◽  
Daniela Cesselli ◽  
Masaaki Hidaka ◽  
...  

Author(s):  
Wenhui Huang ◽  
Xuefeng Gu ◽  
Yingying Wang ◽  
Yuhan Bi ◽  
Yu. Yang ◽  
...  

1991 ◽  
Vol 69 (3) ◽  
pp. 414-418 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas

Previous investigations have shown that the activation of δ-opioid receptors depresses the release of acetylcholine (ACh) in the rat caudate putamen. This finding raised the possibility that the release of ACh is similarly modulated in the globus pallidus, a region containing a distinct population of cholinergic neurons and enriched in enkephalinergic nerve terminals. In the present study the pallidal release of ACh was characterized and the effects of δ-opioid receptor activation on this release were examined. The results show that this release is stimulated by high K+ in a concentration- and Ca2+-dependent manner. D-Pen2,L-Pen5-enkephalin (0.1 – 10 μM), a selective δ-opioid receptor agonist, produced a dose-related inhibition of the 25 mM K+-evoked tritium release. The maximal inhibitory effect, representing a 34% decrease in the K+-induced tritium release, was observed at a concentration of 1 μM. This opioid effect was attenuated by the selective δ-opioid receptor antagonist, ICI 174864 (1 μM). These findings support the role of a δ-opioid receptor in the modulation of ACh release in the rat globus pallidus.Key words: globus pallidus, acetylcholine, enkephalin, release.


Sign in / Sign up

Export Citation Format

Share Document