Impact of chronic hyperglycemia on Small Heat Shock Proteins in diabetic rat brain

• Published in: Archives of biochemistry and biophysics 2021-04, Vol.701, p.108816-108816, Article 108816
• Main Authors: Reddy, V. Sudhakar, Pandarinath, S., Archana, M., Reddy, G. Bhanuprakash
• Format: Article
• Language: English
• Subjects: Amyloidogenic proteins; Animals; Brain - metabolism; Brain - pathology; Cerebral cortex; Chronic Disease; Diabetes; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Gene Expression Regulation; Heat shock transcription factors; Heat-Shock Proteins, Small - biosynthesis; Hyperglycemia - metabolism; Hyperglycemia - pathology; Male; Nerve Tissue Proteins - biosynthesis; Rats; Rats, Sprague-Dawley; Small heat shock proteins; Streptozotocin
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2021.108816

Small heat shock proteins (sHsps) are a family of proteins. Some are induced in response to multiple stimuli and others are constitutively expressed. They are involved in fundamental cellular processes, including protein folding, apoptosis, and maintenance of cytoskeletal integrity. Hyperglycemia created during diabetes leads to neuronal derangements in the brain. In this study, we investigated the impact of chronic hyperglycemia on the expression of sHsps and heat shock transcription factors (HSFs), solubility and aggregation of sHsps and amyloidogenic proteins, and their role in neuronal apoptosis in a diabetic rat model. Diabetes was induced in Sprague–Dawley rats with streptozotocin and hyperglycemia was maintained for 16 weeks. Expressions of sHsps and HSFs were analyzed by qRT-PCR and immunoblotting in the cerebral cortex. Solubility of sHsps and amyloidogenic proteins, including α-synuclein and Tau, was analyzed by the detergent soluble assay. Neuronal cell death was analyzed by TUNEL staining and apoptotic markers. The interaction of sHsps with amyloidogenic proteins and Bax was assessed using co-immunoprecipitation. Hyperglycemia decreased Hsp27 and HSF1, and increased αBC, Hsp22, and HSF4 levels at transcript and protein levels. Diabetes induced the aggregation of αBC, Hsp22, α-synuclein, and pTau, as their levels were higher in the insoluble fraction. Additionally, diabetes impaired the interaction of αBC with α-synuclein and pTau. Furthermore, diabetes reduced the interaction of αBC with Bax, which may possibly contribute to neuronal apoptosis. Together, these results indicate that chronic hyperglycemia induces differential responses of sHsps by altering their expression, solubility, interaction, and roles in apoptosis. •Diabetes significantly increased the levels of αB-crystallin (αBC), Hsp22, HSF4 while decreased the Hsp27 and HSF1.•Diabetes induced the aggregation of αBC, Hsp22, α-synuclein, pTau by reducing their solubility.•Diabetes impaired the interaction of αBC with α-synuclein, and pTau.•Diabetes increased the neuronal apoptosis and reduced the interaction of αBC with Bax.