Knockdown of Heat Shock Proteins HSPA6 (Hsp70B') and HSPA1A (Hsp70-1) Sensitizes Differentiated Human Neuronal Cells to Cellular Stress.

Neurochemical Research
Catherine A S Deane, Ian R Brown

Abstract

Heat shock proteins are involved in cellular repair and protective mechanisms that counter characteristic features of neurodegenerative diseases such as protein misfolding and aggregation. The HSPA (Hsp70) multigene family includes the widely studied HSPA1A (Hsp70-1) and the little studied HSPA6 (Hsp70B') which is present in the human genome and not in mouse and rat. The effect of knockdown of HSPA6 and HSPA1A expression was examined in relation to the ability of differentiated human SH-SY5Y neuronal cells to tolerate thermal stress. Low dose co-application of celastrol and arimoclomol, which induces Hsps, enhanced the ability of differentiated neurons to survive heat shock. Small interfering RNA (siRNA) knockdown of HSPA6 and HSPA1A resulted in loss of the protective effect of co-application of celastrol/arimoclomol. More pronounced effects on neuronal viability were apparent at 44 °C heat shock compared to 43 °C. siRNA knockdown suggests that HSPA6 and HSPA1A contribute to protection of differentiated human neuronal cells from cellular stress.

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Citations

Jan 25, 2018·International Journal of Molecular Sciences·Botond PenkeLászló Vígh
Nov 10, 2018·Journal of Alzheimer's Disease : JAD·Catherine A S Deane, Ian R Brown
Oct 6, 2020·Frontiers in Cellular Neuroscience·Erin N Lottes, Daniel N Cox
Mar 20, 2019·Birth Defects Research·Franziska KauseHeiko Reutter
May 20, 2021·Journal of Medicinal Chemistry·Andrew J Ambrose, Eli Chapman
Dec 7, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Zicong XieDaxin Pang

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Methods Mentioned

BETA
transfection
Protein Assay

Software Mentioned

Volocity 3D
Quantity One ® 1 - D Analysis

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