Stress protein and proto-oncogene expression as indicators of neuronal pathophysiology after ischemia.
Induction of hsp70 mRNA and protein appear to provide useful markers for delineating stages in the progression of neuronal pathophysiology after ischemia. Detection of hsp70 encoded by the induced mRNA is dependent on complex interactions between the time course of mRNA expression and recovery of protein synthesis in a given neuron population, and perhaps other factors relating to specific aspects of hsp70 physiology, during recirculation intervals of hours to days. Transient mRNA expression and subsequent detection of immunoreactive hsp70 protein appear to identify neurons more likely to survive ischemia and other insults, while prolonged expression of hsp70 mRNA is associated with more severe neuronal injury. Fos and Jun immunoreactivities are also increased after ischemia, and provide indexes of functional gene expression during earlier recirculation periods. The accumulation of Fos immunoreactivity in particular designates neurons in which rapid recovery of protein synthesis during 1-3 h recirculation has allowed translation of the very transiently expressed c-fos mRNA. Jun-like immunoreactivity allows an evaluation of events at later recirculation intervals, and provides a clear demonstration of synthesis and accumulation of induced protein in CA1 neurons at 6 h following 2 min ischemia. Detailed understanding of the significance of such interactions between transcriptional and translational events will continue to evolve as information accumulates regarding the expression of additional mRNAs and proteins after ischemia. The present demonstration that Jun-like immunoreactivity accumulates in CA1 neurons after brief ischemia indicates that widespread changes in gene expression, expected as a consequence of such primary effects on transcription factor activity, are likely to contribute to the phenomenon of induced ischemic tolerance and to other persistent changes in the brain following diverse insults.
Nowak
T S
TS
Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Osborne
O C
OC
Suga
S
S
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes
D006360:Heat-Shock Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas