Aims: The preservation of pancreatic β-cell function is a key point in the treatment of type 2 diabetes mellitus. There is substantial evidence demonstrating that heat-shock protein 90 (Hsp90) is needed for the stabilization and correct folding of client proteins and plays important roles in various biological processes. Here, we revealed the important role of Hsp90 in β-cell function.
Methods: Islets from male Sprague-Dawley rats were isolated to be used for further RT-PCR, Western blot, and insulin secretion test ex vivo in response to different stimuli.
Results: Our results revealed that Hsp90 expression was significantly decreased in isolated rat islets exposed to high glucose, which was involved in glucokinase activation and glucose metabolism, not calcium signaling. Two kinds of Hsp90 inhibitors 17-DMAG and CCT018159 markedly enhanced glucose-stimulated insulin secretion from rat islets, along with increased expressions of genes closely related to β-cell function.
Conclusions: These data indicate that Hsp90 may be involved in high glucose-induced islet function adaptation.
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http://dx.doi.org/10.1007/s00592-016-0852-2 | DOI Listing |
Background: A significant proportion of individuals maintain healthy cognitive function despite having extensive Alzheimer's disease (AD) pathology, known as cognitive resilience. Understanding the molecular mechanisms that protect these individuals can identify therapeutic targets for AD dementia. This study aims to define molecular and cellular signatures of cognitive resilience, protection and resistance, by integrating genetics, bulk RNA, and single-nucleus RNA sequencing data across multiple brain regions from AD, resilient, and control individuals.
View Article and Find Full Text PDFComp Biochem Physiol C Toxicol Pharmacol
January 2025
Department of Zoology, University of Kerala, Kariavattom, Thiruvananthapuram 695581, Kerala, India; Inter-University Centre for Evolutionary and Integrative Biology-iCEIB, School of Life Sciences, University of Kerala, Kariavattom, Thiruvananthapuram 695 581, Kerala, India; Sastrajeevan Integrative Project, Centre for Integrative Stress and Ease-cRISE, Gregorian College of Advanced Studies, Sreekariyam, Thiruvananthapuram 695017, Kerala, India. Electronic address:
The cardiac actin cytoskeleton has a dynamic pattern of polymerisation. It is uncertain how far actin destabilisation impacts mitochondrial energetics and biogenesis, cell signal status, and structural entities in cardiomyocytes, particularly in hypoxic conditions. We thus tested the in vitro action of cytochalasin D (Cyt D), an inhibitor of actin polymerisation, in hypoxic ventricular explants to elucidate the role of the actin in mitochondrial energetics and biogenesis, cell signals and actin/tubulin/hsps/MMPs dynamics in hypoxic air-breathing fish hearts.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Research and Enterprise, University of Cyberjaya, Persiaran Bestari, Cyber 11, 63000, Cyberjaya, Selangor, Malaysia.
As a promising candidate for tackling drug-resistant cancers, triptolide, a diterpenoid derived from the Chinese medicinal plant Tripterygium wilfordii, has been developed. This review summarizes potential antitumor activities, including the suppression of RNA polymerase II, the suppression of heat shock proteins (HSP70 and HSP90), and the blockade of NF-kB signalling. Triptolide is the first known compound to target cancer cells specifically but spare normal cells, and it has success in treating cancers that are difficult to treat, including pancreatic, breast, and lung cancers.
View Article and Find Full Text PDFBiomolecules
December 2024
Laboratory for Molecular Structural Dynamics, Theory Department, National Institute of Chemistry, Hajdrihova 19, p.p. 660, SI-1001 Ljubljana, Slovenia.
Human heat shock protein 90 (Hsp90) is one of the most important chaperones that play a role in the late stages of protein folding. Errors in the process of the chaperone cycle can lead to diseases such as cancer and neurodegenerative diseases. Therefore, the activity of Hsp90 must be carefully regulated.
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