Blog
About

25
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Mechanism underlying berberine’s effects on HSP70/TNF α under heat stress: Correlation with the TATA boxes

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Heat stress can stimulate an increase in body temperature, which is correlated with increased expression of heat shock protein 70 (HSP70) and tumor necrosis factor α (TNF α). The exact mechanism underlying the HSP70 and TNF α induction is unclear. Berberine (BBR) can significantly inhibit the temperature rise caused by heat stress, but the mechanism responsible for the BBR effect on HSP70 and TNF α signaling has not been investigated. The aim of the present study was to explore the relationship between the expression of HSP70 and TNF α and the effects of BBR under heat conditions, using in vivo and in vitro models. The expression levels of HSP70 and TNF α were determined using RT-PCR and Western blotting analyses. The results showed that the levels of HSP70 and TNF α were up-regulated under heat conditions (40 °C). HSP70 acted as a chaperone to maintain TNF α homeostasis with rising the temperature, but knockdown of HSP70 could not down-regulate the level of TNF α. Furthermore, TNF α could not influence the expression of HSP70 under normal and heat conditions. BBR targeted both HSP70 and TNF α by suppressing their gene transcription, thereby decreasing body temperature under heat conditions. In conclusion, BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments.

          Related collections

          Most cited references 32

          • Record: found
          • Abstract: found
          • Article: not found

          HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine.

          Here, we demonstrate a previously unknown function for the 70-kDa heat-shock protein (HSP70) as a cytokine. HSP70 bound with high affinity to the plasma membrane, elicited a rapid intracellular calcium flux, activated nuclear factor (NF)-kappaB and upregulated the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in human monocytes. Furthermore, two different signal transduction pathways were activated by exogenous HSP70: one dependent on CD14 and intracellular calcium, which resulted in increased IL-1beta, IL-6 and TNF-alpha; and the other independent of CD14 but dependent on intracellular calcium, which resulted in an increase in TNF-alpha but not IL-1beta or IL-6. These findings indicate that CD14 is a co-receptor for HSP70-mediated signaling in human monocytes and are indicative of an previously unrecognized function for HSP70 as an extracellular protein with regulatory effects on human monocytes, having a dual role as chaperone and cytokine.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Hsp70 chaperone dynamics and molecular mechanism.

             P Mayer (2013)
            The chaperone functions of heat shock protein (Hsp)70 involve an allosteric control mechanism between the nucleotide-binding domain (NBD) and polypeptide substrate-binding domain (SBD): ATP binding and hydrolysis regulates the affinity for polypeptides, and polypeptide binding accelerates ATP hydrolysis. These data suggest that Hsp70s exist in at least two conformational states. Although structural information on the conformation with high affinity for polypeptides has been available for several years, the conformation with an open polypeptide binding cleft was elucidated only recently. In addition, other biophysical studies have revealed a more dynamic picture of Hsp70s, shedding light on the molecular mechanism by which Hsp70s assist protein folding. In this review recent insights into the structure and mechanism of Hsp70s are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Ubiquitin-mediated proteolysis of HuR by heat shock.

              The RNA-binding protein HuR regulates the stability and translation of numerous mRNAs encoding stress-response and proliferative proteins. Although its post-transcriptional influence has been linked primarily to its cytoplasmic translocation, here we report that moderate heat shock (HS) potently reduces HuR levels, thereby altering the expression of HuR target mRNAs. HS did not change HuR mRNA levels or de novo translation, but instead reduced HuR protein stability. Supporting the involvement of the ubiquitin-proteasome system in this process were results showing that (1) HuR was ubiquitinated in vitro and in intact cells, (2) proteasome inhibition increased HuR abundance after HS, and (3) the HuR kinase checkpoint kinase 2 protected against the loss of HuR by HS. Within a central, HS-labile approximately 110-amino-acid region, K182 was found to be essential for HuR ubiquitination and proteolysis as mutant HuR(K182R) was left virtually unubiquitinated and was refractory to HS-triggered degradation. Our findings reveal that HS transiently lowers HuR by proteolysis linked to K182 ubiquitination and that HuR reduction enhances cell survival following HS.
                Bookmark

                Author and article information

                Journal
                CJNM
                Chinese Journal of Natural Medicines
                Elsevier
                1875-5364
                20 March 2017
                : 15
                : 3
                : 178-191
                Affiliations
                1MOE (Ministry of Education) Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
                2Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
                3MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA
                Author notes
                *Corresponding authors: DU Li-Jun, Tel: 86-10-62796270, E-mail: lijundu@ 123456mail.tsinghua.edu.cn ; XING Dong-Ming, pharm@ 123456mail.tsinghua.edu.cn

                These authors have no conflict of interest to declare.

                Article
                S1875-5364(17)30034-1
                10.1016/S1875-5364(17)30034-1
                28411686
                Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81374006
                Award ID: 90713043
                Award ID: 81073092
                This work was supported by the National Natural Science Foundation of China (Nos. 81374006, 90713043 and 81073092).

                Comments

                Comment on this article