Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, Brazil.
Published: October 2020
AI Article Synopsis
Article Abstract
Human HSP27 is a small heat shock protein that modulates the ability of cells to respond to heat shock and oxidative stress, and also functions as a chaperone independent of ATP, participating in the proteasomal degradation of proteins. The expression of HSP27 is associated with survival in mammalian cells. In cancer cells, it confers resistance to chemotherapy; in neurons, HSP27 has a positive effect on neuronal viability in models of Alzheimer's and Parkinson's diseases. To better understand the mechanism by which HSP27 expression contributes to cell survival, we expressed human HSP27 in the budding yeast Saccharomyces cerevisiae under control of different mutant TEF promoters, that conferred nine levels of graded basal expression, and showed that replicative lifespan and proteasomal activity increase as well as the resistance to oxidative and thermal stresses. The profile of these phenotypes display a dose-response effect characteristic of hormesis, an adaptive phenomenon that is observed when cells are exposed to increasing amounts of stress or toxic substances. The hormetic response correlates with changes in expression levels of HSP27 and also with its oligomeric states when correlated to survival assays. Our results indicate that fine tuning of HSP27 concentration could be used as a strategy for cancer therapy, and also for improving neuronal survival in neurodegenerative diseases.
As many proteins prioritize functionality over constancy of structure, a proteome is the shortest stave in the Liebig's barrel of cell sustainability. In this regard, both prokaryotes and eukaryotes possess abundant machinery supporting the quality of the proteome in healthy and stressful conditions. This machinery, namely chaperones, assists in folding, refolding, and the utilization of client proteins.
Background: Heat shock protein-27 is the microprotein released from renal parenchyma during diabetic oxidative stress, while microalbumin is the plasma protein that appears in urine in diabetic nephropathy.
Methods: This case-control study was conducted from Jan to Sep 2021 in the Physiology department, BMC, BMCH, Quetta. The current study included 105 patients with an age range from 30-50 years and was divided into three groups: i) a control group of healthy participants, ii) a diabetic risk group: participants without signs of diabetic nephropathy and diabetic duration from 1-5 years, iii) diabetic nephropathy group: participants having >30 mg/dl of v microalbumin in urine and diabetic duration from 5-10 years.
Clinical trials for prostate cancer (PCa) patients have implemented the bipolar androgen therapy (BAT) that includes the treatment with supraphysiological androgen level (SAL). SAL treatment induces cellular senescence in tumor samples of PCa patients and in various PCa cell lines, including castration-resistant PCa (CRPC), and is associated with enhanced phospho-AKT levels. Using an AKT inhibitor (AKTi), the SAL-mediated cell senescence is inhibited.
Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer's disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China. Electronic address:
Parkinson's disease (PD) is characterized by the accumulation of misfolded α-synuclein (α-syn). Promoting the degradation of misfolded proteins has been shown to be an effective approach to alleviate PD. This review highlights the roles of specific heat shock proteins (HSPs) in modulating α-syn aggregation and neuronal survival.
