Abstract
Many heat shock proteins are chaperones that help refold or degrade misfolded proteins and battle apoptosis. Because of their capacity to protect against protein misfolding, they may help keep diseases of aging at bay. A few reports have examined heat shock proteins (eg. Hsp25, Hsp60, Hsp70, and heat shock cognate 70 or Hsc70) as a function of age in the striatum and nigra. In the present study, we examined the impact of aging on Hsp25, heme oxygenase 1 (HO1 or Hsp32), Hsp40, Hsp60, Hsc70, Hsc/Hsp70 interacting protein (Hip), 78 kDa glucose-regulated protein (GRP78), Hsp90, and ubiquitinated proteins in the nigra and striatum of the female rat by infrared immunoblotting. Female animals are not typically examined in aging studies, adding further to the novelty of our study. Striatal HO1 and Hsp40 were both higher in middle-aged females than in the oldest group. Hsp60 levels were also highest in middle age in the nigra, but were highest in the oldest animals in the striatum. Striatal levels of Hsc70 and the co-chaperone Hip were lower in the oldest group relative to the youngest animals. In contrast, Hsp25 rose with advancing age in both regions. Hsp25 was also colocalized with tyrosine hydroxylase in nigral neurons. Ubiquitinated proteins exhibited a trend to rise in the oldest animals in both regions, and K48 linkage-specific ubiquitin rose significantly from 4–6 to 16–19 months in the striatum. Our study reveals a complex array of age-related changes in heat shock proteins. Furthermore, the age-related rises in some proteins, such as Hsp25, may reflect endogenous adaptations to cellular stress.
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Acknowledgments
R.K.L wrote the manuscript with A.M.G. A.M.G., S.H., D.B.P., and J.M.P. performed the experiments and analyzed the data. We are grateful to Deb Willson, Mary Caruso, and Jackie Farrer for outstanding administrative support and to Dr. John Pollock for use of his confocal microscope. Funding was provided by the Mylan School of Pharmacy at Duquesne University.
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A.M. Gleixner and S.H. Pulugulla did equivalent work.
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Gleixner, A.M., Pulugulla, S.H., Pant, D.B. et al. Impact of aging on heat shock protein expression in the substantia nigra and striatum of the female rat. Cell Tissue Res 357, 43–54 (2014). https://doi.org/10.1007/s00441-014-1852-6
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DOI: https://doi.org/10.1007/s00441-014-1852-6