Characterization and regulation of cold-induced heat shock protein expression in mouse brown adipose tissue.
The accumulation of heat shock proteins (HSPs) after the exposure of cells or organisms to elevated temperatures is well established. It is also known that a variety of other environmental and cellular metabolic stressors can induce HSP synthesis. However, few studies have investigated the effect of cold temperature on HSP expression. Here we report that exposure of Institute of Cancer Research (ICR) mice to cold ambient temperatures results in a tissue-selective induction of HSPs in brown adipose tissue (BAT) coincident with the induction of mitochondrial uncoupling protein synthesis. Cold-induced HSP expression is associated with enhanced binding of heat shock transcription factors to DNA, similar to that which occurs after exposure of cells or tissues to heat and other metabolic stresses. Adrenergic receptor antagonists were found to block cold-induced HSP70 expression in BAT, whereas adrenergic agonists induced BAT HSP expression in the absence of cold exposure. These findings suggest that norepinephrine, released in response to cold exposure, induces HSP expression in BAT. Norepinephrine appears to initiate transcription of HSP genes after binding to BAT adrenergic receptors through, as yet, undetermined signal transduction pathways. Thermogenesis results from an increase in activity and synthesis of several metabolic enzymes in BAT of animals exposed to cold challenge. The concomitant increase in HSPs may function to facilitate the translocation and activity of the enzymes involved in this process.
Matz
J M
JM
Department of Pharmacology and Toxicology, University of North Dakota, Grand Forks 58202, USA.
Blake
M J
MJ
Tatelman
H M
HM
Lavoi
K P
KP
Holbrook
N J
NJ
D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics; D003080:Cold Temperature; D004247:DNA / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D004247:DNA