Embryonic lethal abnormal vision proteins and adenine and uridine-rich element mRNAs after global cerebral ischemia and reperfusion in the rat

Wang, Haihui; Anggraini, Fika Tri; DeGracia, Donald J.

doi:10.1177/0271678x16657572

Cited by 8 publications

(8 citation statements)

References 79 publications

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“…This allowed us to expand the list of ARE‐mRNA to 1592 transcripts, against which the results of study 2 were compared. Study 2 showed 19 and 46% of polysome‐associated mRNAs contained ARE sequences in CA1 and CA3, respectively, an approximately twofold increase in CA3 over CA1 at 8R . The increased sensitivity to detect ARE‐mRNAs in study 2 compared with study 1 can be attributed to the expanded ARE‐mRNA list and to the use of Rat Gene ST 2.0 chips, which detected a greater number of probes than Rat Gene ST 1.0 chips.…”

Section: Postischemic Ribonomicsmentioning

confidence: 95%

“…In addition, small sets of RBPs were detected on polysome pellets or coprecipitated with ELAV proteins from the experimental groups . These sets were different for each experimental group and only PABP was found in all groups on polysome pellets.…”

Section: Postischemic Ribonomicsmentioning

confidence: 95%

“…Other transcription‐dependent stress responses are activated: the HIF response, the ER UPR, the mitochondrial UPR, antioxidant pathways, and DNA repair pathways . Hundreds to thousands of genes change in response to I/R injury …”

Section: Delayed Neuronal Deathmentioning

confidence: 99%

“…We used liquid chromatography tandem mass spectroscopy (LC‐MS/MS) to evaluate RBPs associated with either (1) polysome pellets isolated by sucrose pad or (2) after immunoprecipitation (IP) using an antisera that detected all four Hu isoforms . We obtained a rather startling result: HuB, HuC, and HuD proteins were not detected in control CA1 polysome pellets or after IP with the ELAV antisera.…”

Section: Postischemic Ribonomicsmentioning

confidence: 99%

“…RNA extraction from the top of the gradient was taken as polysome unbound (U) RNAs. In study 2, total (T) RNA was extracted from an aliquot of PMS. Polysome pellets were isolated from the remaining PMS by sucrose pad, and polysome pellet‐associated (P) RNA was extracted.…”

Section: Postischemic Ribonomicsmentioning

confidence: 99%

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Regulation of mRNA following brain ischemia and reperfusion

DeGracia

2017

WIREs RNA

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There is growing appreciation that mRNA regulation plays important roles in disease and injury. mRNA regulation and ribonomics occur in brain ischemia and reperfusion (I/R) following stroke and cardiac arrest and resuscitation. It was recognized over 40 years ago that translation arrest (TA) accompanies brain I/R and is now recognized as part of the intrinsic stress responses triggered in neurons. However, neuron death correlates to a prolonged TA in cells fated to undergo delayed neuronal death (DND). Dysfunction of mRNA regulatory processes in cells fated to DND prevents them from translating stress-induced mRNAs such as heat shock proteins. The morphological and biochemical studies of mRNA regulation in postischemic neurons are discussed in the context of the large variety of molecular damage induced by ischemic injury. Open issues and areas of future investigation are highlighted. A sober look at the molecular complexity of ischemia-induced neuronal injury suggests that a network framework will assist in making sense of this complexity. The ribonomic network sits between the gene network and the various protein and metabolic networks. Thus, targeting the ribonomic network may prove more effective at neuroprotection than targeting specific molecular pathways, for which all efforts have failed to the present time to stop DND in stroke and after cardiac arrest. WIREs RNA 2017, 8:e1415. doi: 10.1002/wrna.1415 For further resources related to this article, please visit the WIREs website.

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Section: Postischemic Ribonomicsmentioning

confidence: 95%

Section: Postischemic Ribonomicsmentioning

confidence: 95%

Section: Delayed Neuronal Deathmentioning

confidence: 99%

Section: Postischemic Ribonomicsmentioning

confidence: 99%

Section: Postischemic Ribonomicsmentioning

confidence: 99%

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Regulation of mRNA following brain ischemia and reperfusion

DeGracia

2017

WIREs RNA

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RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders

Guha

Husain

et al. 2022

Glia

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A major hallmark of neuroinflammation is the activation of microglia and astrocytes with the induction of inflammatory mediators such as IL-1β, TNF-α, iNOS, and IL-6.Neuroinflammation contributes to disease progression in a plethora of neurological disorders ranging from acute CNS trauma to chronic neurodegenerative disease.Posttranscriptional pathways of mRNA stability and translational efficiency are major drivers for the expression of these inflammatory mediators. A common element in this level of regulation centers around the adenine-and uridine-rich element (ARE) which is present in the 3 0 untranslated region (UTR) of the mRNAs encoding these inflammatory mediators. (ARE)-binding proteins (AUBPs) such as Human antigen R (HuR), Tristetraprolin (TTP) and KH-type splicing regulatory protein (KSRP) are key nodes for directing these posttranscriptional pathways and either promote (HuR) or suppress (TTP and KSRP) glial production of inflammatory mediators. This review will discuss basic concepts of ARE-mediated RNA regulation and its impact on glial-driven neuroinflammatory diseases. We will discuss strategies to target this novel level of gene regulation for therapeutic effect and review exciting preliminary studies that underscore its potential for treating neurological disorders.

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Disease of mRNA Regulation: Relevance for Ischemic Brain Injury

DeGracia

2017

Transl. Stroke Res.

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In this mini-review we give an overview of the role of mRNA-binding proteins and their associated messenger ribonucleoprotein complexes (mRNPs) in several disease states, and bring this information to bear on the pathophysiology of brain ischemia. One conclusion reached is that mRNPs may play a causal role in proteotoxicity instead of being merely passive targets. Ischemia therapies targeting mRNPs have advantages over targeting single pathways, but the behavior of mRNPs needs to be considered in the design of therapies.

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Embryonic lethal abnormal vision proteins and adenine and uridine-rich element mRNAs after global cerebral ischemia and reperfusion in the rat

Cited by 8 publications

References 79 publications

Regulation of mRNA following brain ischemia and reperfusion

Regulation of mRNA following brain ischemia and reperfusion

RNA regulation of inflammatory responses in glia and its potential as a therapeutic target in central nervous system disorders

Disease of mRNA Regulation: Relevance for Ischemic Brain Injury

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