Delta opioid peptide [d-Ala2, d-Leu5] enkephalin (DADLE) triggers postconditioning against transient forebrain ischemia

Wang, Shuyan; Duan, Yale; Su, Diansan; Wen, Li; Tan, Juan; Yang, Danqing; Wang, Weili; Zhao, Zheng; Wang, Xiangrui

doi:10.1016/j.ejphar.2011.02.006

Cited by 39 publications

(35 citation statements)

References 24 publications

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“…Studies have found that the agonist of the δ-opioid receptor stimulates the proliferation of neonatal rat cardiac myocytes (5) and mimics the protective effects of ischemic preconditioning on heart and brain tissue (6,7). These findings have demonstrated that the δ-opioid receptor plays a significant role in the growth and maintenance of cells.…”

Section: Introductionmentioning

confidence: 86%

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

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Abstract. Apoptosis of human liver cells is commonly found in liver diseases and liver surgery and directly affects their prognosis. Recent studies have found that δ-opioid receptors, abundant in the membranes of hepatic cells, participate in the oncogenesis and progression of liver tumors, viral hepatitis, liver cirrhosis and other diseases. The purpose of this study was to analyze the effect of the activation of the δ-opioid receptor on liver cell apoptosis and explore its relationship with PKC and the mitochondrial pathway. Hepatic cells were serum-deprived to induce apoptosis in vitro. During the period of apoptosis, mitochondrial membrane potential decreased, protein levels of cytosolic cytochrome c increased and the expression of Bcl-2 decreased, indicating that apoptosis was specifically induced by the mitochondrial pathway. Importantly, activation of δ-opioid receptors reversed the apoptotic state of hepatic cells. Following δ-opioid receptor activation, the mitochondrial membrane potential remained stable, and the expression of cytosolic cytochrome c and Bax decreased. These data suggest that δ-opioid receptor activation specifically inhibits the mitochondrial apoptotic pathway. In addition, activation of the δ-opioid receptor apparently increased the levels of PKC; blocking the PKC pathway led to increased apoptosis of liver cells, which was not affected by the activation of δ-opioid receptor. Blocking the PKC pathway led to increased apoptosis of liver cells, which was associated with δ-opioid receptor activation. Therefore, the PKC pathway is involved in the anti-apoptotic effects of the δ-opioid receptor on liver cells.

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Section: Introductionmentioning

confidence: 86%

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

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“…Moreover, the neuroprotective properties of opioids have been recognized recently [14]. Activation of δ opioid receptors (δORs) has been shown to have neuroprotective effect against cerebral ischemia in rats [15]–[18]. In addition, opioid-mediated signaling is implicated in cell survival [19]–[21], and in protection of motor networks during perinatal ischemia [22].…”

Section: Introductionmentioning

confidence: 99%

Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease

et al. 2013

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The reduction of pre-enkephalin (pENK) mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington’s disease (HD), due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing) neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2)-containing green fluorescence protein (GFP)-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

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“…Second, the mechanisms of drug-induced hypothermia are more complicated than simple physical cooling; some of the drugs not only elicit hypothermia but also promote other protective pathways, including anti-inflammatory and anti-apoptotic ones [50,105,129]. Thus, the neuroprotective effects conferred by these drugs may only be correlated with hypothermia instead of being caused by it.…”

Section: Summary and Considerationsmentioning

confidence: 99%

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

Zhang¹,

Wang²,

Zhao³

et al. 2013

CNSNDDT

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Ischemic stroke is a common neurological disorder lacking a cure. Recent studies show that therapeutic hypothermia is a promising neuroprotective strategy against ischemic brain injury. Several methods to induce therapeutic hypothermia have been established; however, most of them are not clinically feasible for stroke patients. Therefore, pharmacological cooling is drawing increasing attention as a neuroprotective alternative worthy of further clinical development. We begin this review with a brief introduction to the commonly used methods for inducing hypothermia; we then focus on the hypothermic effects of eight classes of hypothermia-inducing drugs: the cannabinoids, opioid receptor activators, transient receptor potential vanilloid, neurotensins, thyroxine derivatives, dopamine receptor activators, hypothermia-inducing gases, adenosine, and adenine nucleotides. Their neuroprotective effects as well as the complications associated with their use are both considered. This article provides guidance for future clinical trials and animal studies on pharmacological cooling in the setting of acute stroke. KeywordsBrain ischemia; Hypothermic; Neuroprotection; Pharmacological cooling Send correspondence to: Dr. Feng Zhang, Department of Neurology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, PA, 15213, USA, Telephone: 412-383-7604, Fax: 412-648-1239, zhanfx2@upmc.edu NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 1. Hypothermia and strokes IntroductionTherapeutic hypothermia is defined as a 2-6°C reduction of core body temperature [1][2][3] and is a promising neuroprotective approach against brain injury induced by strokes. In hemorrhagic stroke, hypothermia reduces brain edema [4,5] and improves neurologic function [4][5][6][7]. In ischemic stroke, hypothermia is also protective, which has been proven in randomized clinical trials in human cardiac arrest and in animal studies of focal and global ischemia [8,9]. However, the impact of hypothermia on patients with acute ischemic stroke still needs to be explored [10]. During the past decades, studies on hypothermia and ischemic stroke have suggested that the required amplitude of protective hypothermia depends on its time of initiation relative to stroke onset, duration, and depth of hypothermia [1,9,11]. Optimal protection is typically gained when hypothermia is induced as early as possible after stroke onset, with a mild-to-moderate hypothermia of 32 to 35°C that lasts at least one to two hours [1, 2, 12-14]. Protective mechanism of hypothermia in ischemic strokeAlthough hypothermia is effective in protecting against experimental models of ischemic stroke, the precise protective mechanisms are not yet fully understood. It has been suggested that the protective mechanisms are multifold, including reductions in metabolic rate, cerebral blood flow, blood-brain barrier damage, as well as decreases in excitotoxicity, apoptosis, inflammation and free radical production [15]. On average, hypothermia red...

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Delta opioid peptide [d-Ala2, d-Leu5] enkephalin (DADLE) triggers postconditioning against transient forebrain ischemia

Cited by 39 publications

References 24 publications

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Striatal Pre-Enkephalin Overexpression Improves Huntington’s Disease Symptoms in the R6/2 Mouse Model of Huntington’s Disease

Drug-Induced Hypothermia in Stroke Models: Does it Always Protect?

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