Exercise training and experimental diabetes modulate heat shock protein response in brain

Lappalainen, Zekine; Lappalainen, Jani; Oksala, Niku; Laaksonen, David E.; Khanna, Savita; Sen, Chandan K.; Atalay, Mustafa

doi:10.1111/j.1600-0838.2008.00872.x

Cited by 15 publications

(15 citation statements)

References 44 publications

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“…However, despite the improved exercise tolerance, a lower HSP72 protein response was observed compared to non‐diabetic animals (55% vs 250% relative increase in the present study). The ability of exercise training to increase kidney HSP72 levels is in line with reports in other tissues . It should be noted that that the exercise‐induced HSP responses are dependent on exercise intensity and duration, reflecting a physiological response to the heat shock and oxidative stress of exercise.…”

Section: Discussionsupporting

confidence: 85%

Suppressed heat shock protein response in the kidney of exercise‐trained diabetic rats

Lappalainen

Oksala

Laaksonen

et al. 2018

Scandinavian Med Sci Sports

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Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.

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Section: Discussionsupporting

confidence: 85%

Suppressed heat shock protein response in the kidney of exercise‐trained diabetic rats

Lappalainen

Oksala

Laaksonen

et al. 2018

Scandinavian Med Sci Sports

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“…Lower levels of HSP expression in insulin sensitive tissues, such as muscle and heart, have been reported (Atalay et al 2004;Hooper 2007). Atalay and coworkers recently reported impaired rise in HSP70 protein in exercising diabetic animals, when there was an increased mRNA expression in these subjects (Lappalainen et al 2008). However, increased levels of HSP70 and HSP60 have been reported in the kidney (Atalay et al 2009;Oksala et al 2007) and liver (Oksala et al 2006) of diabetic animals, respectively.…”

Section: Discussionmentioning

confidence: 97%

Increased serum HSP70 levels are associated with the duration of diabetes

Nakhjavani

Morteza

Khajeali

et al. 2010

Cell Stress and Chaperones

105

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The evolutionary conserved family of heat shock proteins (HSP) is responsible for protecting cells against different types of stress, including oxidative stress. Although the levels of HSPs can be readily measured in blood serum, the levels of HSP70 in patients with different durations of diabetes have not been studied before. We quantified serum HSP70 levels in a healthy control group (n=36) and two groups of type 2 diabetic patients, defined as newly diagnosed diabetes (n=36) and patients with diabetes duration of more than 5 years (n=37). The clinical characteristics and biochemical parameters were evaluated in the studied population. We found that serum HSP70 levels were significantly higher in patients with diabetes when compared with controls (p<0.001) and it was higher in patients with disease for more than 5 years than in newly diagnosed patients (p<0.001). Serum HSP70 was inversely correlated with fasting blood sugar in patients with diabetes for more than 5 years (r=−0.500, p=0.002), positively correlated with the history of hypertension in newly diagnosed patients (p<0.001), and positively correlated with age in patients with diabetes (r=0.531, p=0.001). Serum level of HSP70 is significantly higher in patients with diabetes and correlates with the duration of disease. Higher HSP70 in prolonged diabetes versus newly diagnosed diabetes may be an indicator of metabolic derangement in the course of diabetes.

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“…Standard Western blot techniques were used to analyze protein expression in brain, as previously described 10. First, the frozen brains were pulverized under liquid nitrogen with a mortar and sonicated in a buffer containing 25% glycerol, 420 mM NaCl, 1.5 mM MgCl 2 , 0.2 nM EDTA, 20 mM HEPES, 5 µM DTT, and 5 µM PMSF at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…In diabetes, the expression of HSPs can be impaired 1, 6. However, experimental evidence suggests a protective effect of HSP72 in peripheral diabetic neuropathy,7 although decreased6, 8 or unchanged9 levels have also been described in diabetic tissue, including the brain 10. These discrepancies are likely to be tissue‐dependent and related to the duration or severity of diabetes, or other yet unidentified factors.…”

Section: Introductionmentioning

confidence: 99%

“…In a recent study, we used endurance training as a tool to enhance brain HSP response and showed that exercise training induced HSP response in non‐diabetic animals, but not in diabetic animals at the protein level 10. As a continuation of our investigations, the present study was set forth to test the potency of LA for enhancing brain HSP responses in diabetes, because increased levels of HSPs may act beneficial for brain by increasing resistance to stress‐induced neuronal damage 5.…”

Section: Introductionmentioning

confidence: 99%

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Alpha‐lipoic acid does not alter stress protein response to acute exercise in diabetic brain

Lappalainen

Oksala

et al. 2010

Cell Biochemistry & Function

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Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.

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Exercise training and experimental diabetes modulate heat shock protein response in brain

Cited by 15 publications

References 44 publications

Suppressed heat shock protein response in the kidney of exercise‐trained diabetic rats

Suppressed heat shock protein response in the kidney of exercise‐trained diabetic rats

Increased serum HSP70 levels are associated with the duration of diabetes

Alpha‐lipoic acid does not alter stress protein response to acute exercise in diabetic brain

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