Hypothermic Preconditioning Increases Survival of Purkinje Neurons in Rat Cerebellar Slices after an In Vitro  Simulated Ischemia

2004 ◽  
Vol 100 (2) ◽  
pp. 331-337 ◽  
Author(s):  
Hui-Bih Yuan ◽  
Yueming Huang ◽  
Shuqiu Zheng ◽  
Zhiyi Zuo
Keyword(s):  
Acute Phase ◽  
Time Window ◽  
Mild Hypothermia ◽  
High Mobility ◽  
Ischemic Tolerance ◽  
High Mobility Group ◽  
Simulated Ischemia ◽  
Group I ◽  
Adenosine A1

Background A period of hypothermia before ischemia (hypothermic preconditioning) induces a delayed phase of ischemic tolerance in rat brain. However, whether hypothermic preconditioning induces an acute phase (within a few hours after the hypothermia) of ischemic tolerance remains unknown. This study was designed to determine the time window of the hypothermic preconditioning-induced acute phase of neuroprotection, which is useful information for situations during surgery with anticipated ischemic episodes, and its involved mechanisms. Methods Survival of Purkinje cells in rat cerebellar slices was evaluated after a 20-min oxygen-glucose deprivation (OGD, in vitro simulated ischemia) followed by a 4-h recovery. Mild hypothermia (33 degrees C) for 20 min was applied at various times before the OGD. Results The hypothermia applied immediately to 3 h before the OGD equally effectively reduced OGD-induced Purkinje cell death/injury. Glibenclamide, a selective KATP channel blocker; 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine A1 receptor antagonist; and farnesyl protein transferase inhibitor III, a selective inhibitor to reduce Ras farnesylation, abolished hypothermic preconditioning-induced neuroprotection when applied during the hypothermia. OGD increased the expression of high-mobility group I(Y) proteins, which are nuclear transcription factors to enhance the expression of putatively damaging proteins such as cyclooxygenase-2, in cerebellar slices. This increase was attenuated by hypothermic preconditioning. Conclusions Hypothermic preconditioning induces an acute phase of neuroprotection. This neuroprotection depends on activation of the signaling molecules, adenosine A1 receptors, KATP channels, and Ras. Inhibition of putatively damaging proteins via the effects of hypothermic preconditioning on high-mobility group I(Y) expression may also be involved in hypothermic preconditioning-induced neuroprotection.

Induction of High Mobility Group I Architectural Transcription Factors in Proliferating Vascular Smooth Muscle in vivo and in vitro

1999 ◽  
Vol 31 (12) ◽  
pp. 2199-2205 ◽  
Author(s):  
Michael T Chin ◽  
Andrea Pellacani ◽  
Chung- Ming Hsieh ◽  
Sharon SJ Lin ◽  
Mukesh K Jain ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transcription Factors ◽  
Vascular Smooth Muscle ◽  
High Mobility ◽  
High Mobility Group ◽  
Group I

scholarly journals Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

1999 ◽  
Vol 19 (4) ◽  
pp. 2803-2816 ◽  
Author(s):  
Eliette Bonnefoy ◽  
Marie-Thérèse Bandu ◽  
Janine Doly
Keyword(s):  
Binding Site ◽  
Specific Binding ◽  
High Mobility ◽  
Histone H1 ◽  
High Mobility Group ◽  
Rich Region ◽  
Beta Interferon ◽  
Group I ◽  
Preferential Binding

ABSTRACT The high-mobility-group I (HMGI) protein is a nonhistone component of active chromatin. In this work, we demonstrate that HMGI protein specifically binds to the AT-rich region of the murine beta interferon (IFN-β) promoter localized upstream of the murine virus-responsive element (VRE). Contrary to what has been described for the human promoter, HMGI protein did not specifically bind to the VRE of the murine IFN-β promoter. Stably transfected promoters carrying mutations on this HMGI binding site displayed delayed virus-induced kinetics of transcription. When integrated into chromatin, the mutated promoter remained repressed and never reached normal transcriptional activity. Such a phenomenon was not observed with transiently transfected promoters upon which chromatin was only partially reconstituted. Using UV footprinting, we show that the upstream AT-rich sequences of the murine IFN-β promoter constitute a preferential binding region for histone H1. Transfection with a plasmid carrying scaffold attachment regions as well as incubation with distamycin led to the derepression of the IFN-β promoter stably integrated into chromatin. In vitro, HMGI protein was able to displace histone H1 from the upstream AT-rich region of the wild-type promoter but not from the promoter carrying mutations on the upstream high-affinity HMGI binding site. Our results suggest that the binding of histone H1 to the upstream AT-rich region of the promoter might be partly responsible for the constitutive repression of the promoter. The displacement by HMGI protein of histone H1 could help to convert the IFN-β promoter from a repressed to an active state.

scholarly journals LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein

2021 ◽  
Vol 14 (6) ◽  
pp. 558
Author(s):  
Verena Peek ◽  
Lois M. Harden ◽  
Jelena Damm ◽  
Ferial Aslani ◽  
Stephan Leisengang ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Area Postrema ◽  
High Mobility ◽  
High Mobility Group ◽  
Direct Access ◽  
Significant Release ◽  
Factor Α ◽  
Culture Supernatants

High mobility group box (HMGB)1 action contributes to late phases of sepsis, but the effects of increased endogenous plasma HMGB1 levels on brain cells during inflammation are unclear. Here, we aimed to further investigate the role of HMGB1 in the brain during septic-like lipopolysaccharide-induced inflammation in rats (LPS, 10 mg/kg, i.p.). HMGB-1 mRNA expression and release were measured in the periphery/brain by RT-PCR, immunohistochemistry and ELISA. In vitro experiments with disulfide-HMGB1 in primary neuro-glial cell cultures of the area postrema (AP), a circumventricular organ with a leaky blood–brain barrier and direct access to circulating mediators like HMGB1 and LPS, were performed to determine the direct influence of HMGB1 on this pivotal brain structure for immune-to-brain communication. Indeed, HMGB1 plasma levels stayed elevated after LPS injection. Immunohistochemistry of brains and AP cultures confirmed LPS-stimulated cytoplasmatic translocation of HMGB1 indicative of local HMGB1 release. Moreover, disulfide-HMGB1 stimulation induced nuclear factor (NF)-κB activation and a significant release of interleukin-6, but not tumor necrosis factor α, into AP culture supernatants. However, only a few AP cells directly responded to HMGB1 with increased intracellular calcium concentration. Interestingly, priming with LPS induced a seven-fold higher percentage of responsive cells to HMGB1. We conclude that, as a humoral and local mediator, HMGB1 enhances brain inflammatory responses, after LPS priming, linked to sustained sepsis symptoms.

scholarly journals Defective Calmodulin-Mediated Nuclear Transport of the Sex-Determining Region of the Y Chromosome (SRY) in XY Sex Reversal

2005 ◽  
Vol 19 (7) ◽  
pp. 1884-1892 ◽  
Author(s):  
Helena Sim ◽  
Kieran Rimmer ◽  
Sabine Kelly ◽  
Louisa M. Ludbrook ◽  
Andrew H. A. Clayton ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Nuclear Import ◽  
High Mobility ◽  
Sex Reversal ◽  
High Mobility Group ◽  
Missense Mutations ◽  
Nuclear Localization Signals ◽  
Xy Sex Reversal

Abstract The sex-determining region of the Y chromosome (SRY) plays a key role in human sex determination, as mutations in SRY can cause XY sex reversal. Although some SRY missense mutations affect DNA binding and bending activities, it is unclear how others contribute to disease. The high mobility group domain of SRY has two nuclear localization signals (NLS). Sex-reversing mutations in the NLSs affect nuclear import in some patients, associated with defective importin-β binding to the C-terminal NLS (c-NLS), whereas in others, importin-β recognition is normal, suggesting the existence of an importin-β-independent nuclear import pathway. The SRY N-terminal NLS (n-NLS) binds calmodulin (CaM) in vitro, and here we show that this protein interaction is reduced in vivo by calmidazolium, a CaM antagonist. In calmidazolium-treated cells, the dramatic reduction in nuclear entry of SRY and an SRY-c-NLS mutant was not observed for two SRY-n-NLS mutants. Fluorescence spectroscopy studies reveal an unusual conformation of SRY.CaM complexes formed by the two n-NLS mutants. Thus, CaM may be involved directly in SRY nuclear import during gonadal development, and disruption of SRY.CaM recognition could underlie XY sex reversal. Given that the CaM-binding region of SRY is well-conserved among high mobility group box proteins, CaM-dependent nuclear import may underlie additional disease states.

Analysis of high mobility group I(Y) [HMGI(Y)] proteins expression in pancreatic neoplasms

2000 ◽  
Vol 118 (4) ◽  
pp. A271
Author(s):  
Nobutsugu Abe ◽  
Takashi Watanabe ◽  
Masanori Sugiyama ◽  
Yutaka Atomi
Keyword(s):  
Pancreatic Neoplasms ◽  
High Mobility ◽  
High Mobility Group ◽  
Group I

scholarly journals Does high-mobility-group non-histone protein HMG 1 interact specifically with histone H1 subfractions?

1979 ◽  
Vol 183 (3) ◽  
pp. 657-662 ◽  
Author(s):  
P D Cary ◽  
K V Shooter ◽  
G H Goodwin ◽  
E W Johns ◽  
J Y Olayemi ◽  
...  
Keyword(s):  
Specific Interaction ◽  
High Mobility ◽  
Histone H1 ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Histone Protein ◽  
Total Histone ◽  
Equilibrium Sedimentation ◽  
Histone H5

The interaction of the non-histone chromosomal protein HMG (high-mobility group) 1 with histone H1 subfractions was investigated by equilibrium sedimentation and n.m.r. sectroscopy. In contrast with a previous report [Smerdon & Isenberg (1976) Biochemistry 15, 4242–4247], it was found, by using equilibrium-sedimentation analysis, that protein HMG 1 binds to all three histone H1 subfractions CTL1, CTL2, and CTL3, arguing against there being a specific interaction between protein HMG 1 and only two of the subfractions, CTL1 and CTL2. Raising the ionic strength of the solutions prevents binding of protein HMG 1 to total histone H1 and the three subfractions, suggesting that the binding in vitro is simply a non-specific ionic interaction between acidic regions of the non-histone protein and the basic regions of the histone. Protein HMG 1 binds to histone H5 also, supporting this view. The above conclusions are supported by n.m.r. studies of protein HMG 1/histone H1 subfraction mixtures. When the two proteins were mixed, there was little perturbation of the n.m.r. spectra and there was no evidence for specific interaction of protein HMG 1 with any of the subfractions. It therefore remains an open question as to whether protein HMG 1 and histone H1 are complexed together in chromatin.

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