Hippocampal Responses to Corticosterone and Stress, One of which is the 35,000 M_r Protein, Glycerol Phosphate Dehydrogenase

Abstract

Previously, the synthesis of a hippocampal 35,000 M(r) protein increased in response to glucocorticoid treatment and a variety of stressors. We now show by immunoprecipitation that this cytosolic protein is glycerol 3-phosphate dehydrogenase (E.C.1.1.1.8; GPDH). In addition, four polypeptides encoded by glucocorticoid-induced mRNAs co-migrated with hippocampal protein synthetic products on two-dimensional polyacrylamide gels, including 35,000 M(r) protein of approximately pl 6.3, that had previously been identified as GPDH by hybrid-selection with a GPDH cDNA clone. The 35,000 M(r) in vitro translation product was also immunoprecipitated with the GPDH antibody. Using radiolabeled hippocampal slices and two-dimensional gel analysis, a 35,000 M(r) polypeptide of approximately pl 6.4 increased five-fold after 30 min of intermittent tail-shock. This protein was found predominantly in the 20,000 x g pellet and did not immunoprecipitate with the GPDH antibody. However, a 35,000 M(r) polypeptide was also found in the cytosol as a minor component after stress, which did immunoprecipitate with the GPDH antibody. Therefore, there are at least two shock-induced 35,000 M(r) proteins, one of which is GPDH. These results establish that increases in GPDH mRNA prevalence and protein synthesis occur in response to both glucocorticoids and stress in the adult rat hippocampus. Based on the increased enzyme activity seen in the nervous system in response to glucocorticoids, dietary restriction, and nerve injury, the induction of GPDH may have functional consequences in cellular adaptation to stress.

Regulation of pp60c‐src synthesis in rat hippocampal slices by in vitro ischemia and glucocorticoid administration

“…Glucocorticoid‐mediated downregulation of neither pp60 c‐ src nor of the 78 kDa protein was observed in hippocampal slices that were incubated at 37°C under nonischemic conditions (Schlatter and Dokas, 1989; Nichols et al, 1996). Instead, the in vitro synthesis of a cytosolic 35 kDa protein, glycerol phosphate dehydrogenase (GPDH), is enhanced in hippocampal slices incubated at 37°C after acute treatment with exogenous corticosterone.…”

Seasonal expressed sequence tags of rainbow smelt (Osmerus mordax) revealed by subtractive hybridization and the identification of two genes up-regulated during winter

“…Serum cortisol levels are highly variable over short time intervals (weeksmonths) in smelt and they do not appear to vary seasonally in smelt at ambient temperature, but this interpretation must be viewed with caution as the stress of capture and bleeding may elevate cortical levels in a greater extent than a temperature effect per se (Lewis and Driedzic, unpublished). However, the gene encoding glycerol-3-phosphate dehydrogenase, which appears to drive the winter accumulation of glycerol in smelt, was found to be highly up-regulated in smelt liver during winter (Liebscher et al, 2006) and the same gene has also been shown to respond to cortisol in human glial cells (Nichols et al, 1996) suggesting the possibility of its regulation by cortisol by smelt during winter. Moreover, there is precedent for a role of cortisol in winter adaptation of fish, as temperate populations of killifish (Fundulus heteroclitus) have been shown to increase transcription of lactate dehydrogenase B (an adaptive response) in response to cortisol (Schulte et al, 2000).…”

Glial- and fat-specific expression of the rat glycerol phosphate dehydrogenase-luciferase fusion gene in transgenic mice

“…Experimental stress paradigms such as vibratory stress cause a prominent increase in GPDH mRNA level in oligodendrocytes. The increase is related to increases in endogenous glucocorticoid level (Nichols et al, 1989(Nichols et al, , 1996Masters et al, 1994). Moreover, in the mouse cerebellum, GPDH expression in Bergmann glial cells is also known to be dependent on appropriate contact with neighboring Purkinje cells.…”

“…GPDH expression in oligodendroglial cells is also up-regulated by the steroid hormone glucocorticoids (Kumar et al, 1989). The glucocorticoid induction has been recently correlated to be to a stressinducible event in the brain Nichols et al, 1996), indicating that GPDH is part of the changes in glial metabolism in response to stress or increase in glucocorticoids. Additionally, GPDH expression in Bergmann glia is also dependent on appropriate contact with neighboring Purkinje cells, and thyroid hormone level (Fisher, 1984).…”