Related Experiment Video

Updated: Apr 10, 2026

Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry
10:24

Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry

Published on: June 7, 2018

9.3K

Development-dependent regulation of molecular chaperones after hypoxia-ischemia

Xin Sun1, Robert Crawford2, Chunli Liu2

  • 1Shock Trauma and Anesthesiology Research Center, University of MD School of Medicine, USA; Department of Neurology, The First Teaching Hospital, Jilin University, China.

Neurobiology of Disease
|June 14, 2015
PubMed

Insights

The brain

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cellular Stress Response

Background:

  • Hypoxia-ischemia (HI) affects brain development differently in immature and mature brains.
  • Cellular stress responses are critical for brain injury outcomes.
  • Heat shock proteins (HSPs) are key components of the cellular stress response.

Purpose of the Study:

  • To investigate the developmental differences in cellular stress response following hypoxia-ischemia (HI).
  • To compare the activation of heat-shock transcription factor-1 (HSF1) and molecular chaperone expression in immature versus mature rat brains after HI.

Main Methods:

  • Postnatal day 7 (P7) and P26 rats were subjected to HI.
  • Analysis of HSF1 nuclear accumulation and HSP expression (hsp70, grp78, hsp60) using in situ hybridization, Western blotting, and confocal microscopy.
  • Assessment of molecular chaperone mRNA and protein levels at various recovery periods post-HI.

Main Results:

  • Mature (P26) neurons showed dramatic HSF1 nuclear accumulation and hsp70 mRNA induction post-HI, while immature (P7) neurons showed minimal response.
  • HSF1 levels were significantly higher in P26 compared to P7 brain samples.
  • Induction of ER and mitochondrial chaperones (grp78, hsp60) was moderate and observed only in mature brains.
  • HSP70 protein translation in P26 neurons peaked at 24h, after some neuronal death had occurred.

Conclusions:

  • The cellular stress response to HI is highly development-dependent, being pronounced in mature brains but negligible in neonatal neurons.
  • Therapeutic strategies targeting stress pathways may have differential effectiveness in immature versus mature brains following HI.
  • The delayed induction of molecular chaperones in mature brains might be too late to prevent acute HI injury.

Keywords:
Brain developmentER stressHypoxia–ischemiaMolecular chaperonesNeonatal neuronal deathProtein aggregation

More Related Videos

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions09:17

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions

Published on: August 2, 2018

18.9K
Intracellular Refolding Assay07:18

Intracellular Refolding Assay

Published on: January 24, 2012

14.9K

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
20.9K
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

15.7K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
4.0K
Bacterial Protein Maturation01:26

Bacterial Protein Maturation

Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
713
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
Other Stress Responses in Bacteria01:30

Other Stress Responses in Bacteria

Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
536