Heat-shock protein 70: expression in monocytes of patients with sleep apnoea and association with oxidative stress and tumour necrosis factor-alpha.
Obstructive sleep apnoea (OSA) is associated with a variety of nightly stresses, including intermittent hypoxaemia, oxidative stress and sleep fragmentation. Heat-shock proteins (HSPs) are upregulated in response to an array of environmental and metabolic stresses. We hypothesized that the OSA-related stresses would affect the expression of HSP70 in monocytes. Basal (30 min, at 37 degrees C), heat stress-induced HSP70 (30 min, at 43 degrees C) and basal tumour necrosis factor-alpha (TNF-alpha) were determined by flow cytometry in monocytes of 10 patients with OSA and 10 controls matched by age, gender and body mass index. Oxidative stress was determined by thiobarbituric acid-reactive substances (TBARS) and antioxidant paraoxonase-1 activity. Basal HSP70 expression was 1.8-fold higher in patients with OSA as compared with controls (P < 0.0005) and was significantly positively correlated with TBARS (r = 0.56, P < 0.009). However, induction of HSP70 in response to heat stress treatment was lower by 40% in OSA monocytes as compared with controls (P < 0.0003). Furthermore, heat stress-induced HSP70 expression was significantly negatively correlated with basal HSP70 expression independently of apnoea severity (r = -0.69, P < 0.0006). Also, basal intracellular TNF-alpha expression was inversely correlated with heat-shock-induced HSP70 (r = -0.78, P < 0.015) in OSA monocytes but not in controls. In conclusion, basal HSP70 overexpression that is a protective mechanism indicative of disease-associated stress was significantly higher in patients with OSA and was correlated with oxidative stress. On the other hand, in response to a defined heat-stress treatment, the induction of HSP70 was lower in patients with OSA, indicative of a possible maladaptive response to an acute stress. Correlations with oxidative stress and TNF-alpha further support this conclusion.
Lavie
Lena
L
Lloyd Rigler Sleep Apnea Research Laboratory, Unit of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. lenal@tx.technion.ac.il
Dyugovskaya
Larissa
L
Golan-Shany
Orit
O
Lavie
Peretz
P
D000328:Adult; D005260:Female; D005434:Flow Cytometry; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D012892:Sleep Deprivation / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha