Diazoxide Increases Liver and Kidney HSP25 and HSP70 After Shock and Stroke

O'Sullivan, Joseph; Fu, Dadin; Alam, Hasan B.; McCabe, Joseph T.

doi:10.1016/j.jss.2007.12.750

Cited by 7 publications

(4 citation statements)

References 42 publications

(46 reference statements)

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“…For example, induction of heat shock proteins reduces the nuclear binding of proinflammatory transcription factors, increases the antioxidant capacity of cells [ 32 ], prevents the activation of intrinsic and extrinsic apoptotic pathways [ 33 ], and helps repair organs via a chaperone pathway [ 34 ]. Regardless of what pathways are induced, the essential consequences are that both delayed and classical preconditioning decrease energy demand of ischemic tissues [ 35 ] and ultimately increase cell survival after the insult [ 36 ]. Recently, it has been reported that agmatine exerts neuroprotection against ischemic injury in neuronal cell cultures and experimental stroke in vivo [ 7 13 ].…”

Section: Discussionmentioning

confidence: 99%

Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

Kim

Jung

et al. 2017

Exp Neurobiol

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Ischemic preconditioning (IP) is one of the most important endogenous mechanisms that protect the cells against ischemia-reperfusion (I/R) injury. However, the exact molecular mechanisms remain unclear. In this study, we showed that changes in the level of agmatine were correlated with ischemic tolerance. Changes in brain edema, infarct volume, level of agmatine, and expression of arginine decarboxylase (ADC) and nitric oxide synthases (NOS; inducible NOS [iNOS] and neural NOS [nNOS]) were analyzed during I/R injury with or without IP in the rat brain. After cerebral ischemia, brain edema and infarct volume were significantly reduced in the IP group. The level of agmatine was increased before and during ischemic injury and remained elevated in the early reperfusion phase in the IP group compared to the experimental control (EC) group. During IP, the level of plasma agmatine was increased in the early phase of IP, but that of liver agmatine was abruptly decreased. However, the level of agmatine was definitely increased in the ipsilateral and contralateral hemisphere of brain during the IP. IP also increased the expression of ADC—the enzyme responsible for the synthesis of endogenous agmatine—before, during, and after ischemic injury. In addition, ischemic injury increased endogenous ADC expression in the EC group. The expression of nNOS was reduced in the I/R injured brain in the IP group. These results suggest that endogenous increased agmatine may be a component of the ischemic tolerance response that is induced by IP. Agmatine may have a pivotal role in endogenous ischemic tolerance.

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Section: Discussionmentioning

confidence: 99%

Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

Kim

Jung

et al. 2017

Exp Neurobiol

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“…Studies indicated that morphine could activate K ATP channel [ 33 ], which is an ABC transporter [ 34 ]. Moreover, it was reported that the opening of the K ATP channel could upregulate HSP70 expression [ 35 ]. Hence, we want to investigate whether morphine could induce the release of HSP70 by activating K ATP channel.…”

Section: Introductionmentioning

confidence: 99%

Blocking ATP-sensitive potassium channel alleviates morphine tolerance by inhibiting HSP70-TLR4-NLRP3-mediated neuroinflammation

Tao

Teng

et al. 2017

J Neuroinflammation

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BackgroundLong-term use of morphine induces analgesic tolerance, which limits its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage-associated molecular pattern (DAMP), which was released from various cells upon stimulations under the control of KATP channel and bound with TLR4-inducing inflammation. Glibenclamide, a classic KATP channel blocker, can improve neuroinflammation by inhibiting the activation of NLRP3 inflammasome. Our present study investigated the effect and possible mechanism of glibenclamide in improving morphine tolerance via its specific inhibition on the release of HSP70 and activation of NLRP3 inflammasome induced by morphine.MethodsCD-1 mice were used for tail-flick test to evaluate morphine tolerance. The microglial cell line BV-2 and neural cell line SH-SY5Y were used to investigate the pharmacological effects and the mechanism of glibenclamide on morphine-induced neuroinflammation. The activation of microglia was accessed by immunofluorescence staining. Neuroinflammation-related cytokines were measured by western blot and real-time PCR. The level of HSP70 and related signaling pathway were evaluated by western blot and immunofluorescence staining.ResultsMorphine induced the release of HSP70 from neurons. The released HSP70 activated microglia and triggered TLR4-mediated inflammatory response, leading to the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 and the activation of NLRP3 inflammasome. Moreover, anti-HSP70 neutralizing antibody partly attenuated chronic morphine tolerance. The secretion of HSP70 was under the control of MOR/AKT/KATP/ERK signal pathway. Glibenclamide as a classic KATP channel blocker markedly inhibited the release of HSP70 induced by morphine and suppressed HSP70-TLR4-NLRP3 inflammasome-mediated neuroinflammation, which consequently attenuated morphine tolerance.ConclusionsOur study indicated that morphine-induced extracellular HSP70 was an alternative way for the activation of TLR4-NLRP3 in analgesic tolerance. The release of HSP70 was regulated by MOR/AKT/KATP/ERK pathway. Our study suggested a promising target, KATP channel and a new leading compound, glibenclamide, for treating morphine tolerance.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0997-0) contains supplementary material, which is available to authorized users.

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“…Over the following decades, the investigation of the heat shock response has confirmed that a family of highly conserved HSPs is upregulated following a variety of sublethal stressors, possibly as a result of non-native proteins accumulating in a stressed cell (Voellmy & Boellmann, 2007). These proteins are subcategorized by their molecular weight and are either inherently present or can be induced following sublethal stress (O'Sullivan, et al, 2008). In particular, HSP25 and HSP70 have been thoroughly investigated with the consensus being they are protective when upregulated following stress (Beere, et al, 2000;Garrido, et al, 2006;Takayama, et al, 2003).…”

Section: The Heat Shock Responsementioning

confidence: 99%