Chaperone Hsp70 Content in Dopaminergic Neurons of the Substantia Nigra Increases in Proteasome Dysfunction

• Published in: Neuroscience and behavioral physiology Vol. 43; no. 3; pp. 380 - 387
• Main Authors: Pastukhov, Yu. F., Ekimova, I. V., Guzhova, I. V., Romanova, I. V., Artyukhina, Z. E.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2013; Springer Nature B.V
• Subjects: Age; Alzheimer's disease; Behavioral Sciences; Biomedical and Life Sciences; Biomedicine; Cell cycle; Disease; Enzymes; Homeostasis; Neurobiology; Neurons; Neurosciences; Parkinson's disease; Physiology; Proteins; St Petersburg Russia; Russia; ubiquitin-proteasome system; substantia nigra; neuroprotection; dopaminergic neurons; chaperone Hsp70; rats; lactacystin
• ISSN: 0097-0549; 1573-899X
• DOI: 10.1007/s11055-013-9744-x

Decreases in the activity of the ubiquitin-proteasome system (UPS), which uses up to 90% of cell protein, are regarded as a key mechanism in the development of age-related conformational diseases (Parkinson’s disease (PD), Alzheimer’s disease, and others). Studies in a model of the preclinical stage of PD in Wistar rats showed that the specific UPS inhibitor lactacystin induced degeneration of 24% of dopaminergic neurons in the compact zone of the substantia nigra (czSN), which was almost the same as the proportion of neurons (23%) which in control conditions did not contain the chaperone 70-kDal Heat Shock Protein (Hsp70), which has neuroprotective properties. Of the 77% of neurons which contained Hsp70 in control conditions, 15% lost it in response to lactacystin (which may reduce their resistance to neurotoxin). However, 62% of surviving dopaminergic neurons in the czSN showed a 47% increase in Hsp70 content (which may protect them from degeneration). The increase in Hsp70 content (in czSN tissue) was verified by immunoblotting. Confocal microscopy studies identified partial colocalization of Hsp70 with the key dopamine (DA) synthesis enzyme tyrosine hydroxylase. Thus, moderate weakening of UPS function in czSN, typical of this model of the preclinical stage of PD, was characterized by an increase in the activity of the chaperone system. It is suggested that this process is directed to restoring UPS activity and preserving the dopaminergic neuron population.