Selected Contribution: Differential expression of stress-related genes with aging and hyperthermia

Zhang, Hannah J.; Drake, Victoria J.; Morrison, Joanna; Oberley, Larry W.; Kregel, Kevin C.

doi:10.1152/japplphysiol.00733.2001

Cited by 30 publications

(22 citation statements)

References 32 publications

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“…61). Age-associated regulation of stress-response genes is an area of accelerated research, particularly with the advent of microarray technology (63). The information resulting from such research, in addition to the advances in the area of gene therapy, will be valuable in defining the roles of HSPs and other components of the stress response in aging.…”

Section: Discussionmentioning

confidence: 99%

“…Cells have evolved complex genetic systems to detect specific forms of stress and activate the expression of genes whose products increase the resistance of the cell to further stress and/or initiate the processes of tissue regeneration. Unfortunately, the expression of many of these genes is attenuated in aging (53,63). As a consequence, cellular responsiveness to stress diminishes with advancing age.…”

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confidence: 99%

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Age and attenuation of exercise-induced myocardial HSP72 accumulation

Demirel¹,

Hamilton²,

Shanely³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Overexpression of heat shock protein (HSP)72 is associated with cardioprotection. Hyperthermiainduced HSP72 overexpression is attenuated with senescence. While exercise also increases myocardial HSP72 in young animals, it is unknown whether this effect is attenuated with aging. Therefore, we investigated the effect of aging on exercise-induced myocardial heat shock factor (HSF)-1 activation and HSP72 expression. Male Fischer-344 rats (6 or 24 mo) were randomized to control, exercise, and hyperthermic groups. Exercise consisted of 2 days of treadmill running (60 min/day, ϳ75% maximal oxygen consumption). Hyperthermia, 15 min at ϳ41°C (colonic temperature), was achieved using a temperature-controlled heating blanket. Analyses included Western blotting for myocardial HSP72 and HSF-1, electromobility shift assays for HSF-1 activation, and Northern blotting for HSP72 mRNA. Exercise and hyperthermia increased (P Ͻ 0.05) myocardial HSP72 in both young (Ͼ3.5-and 2.5-fold, respectively) and aged (Ͼ3-and 1.5-fold, respectively) animals. Both exercise and hyperthermic induction of HSP72 was attenuated with age. Myocardial HSF-1 protein, HSF-1 activation, and HSP72 mRNA did not differ with age. These data demonstrate that aging is associated with diminished exercise-induced myocardial HSP72 expression. Mechanisms other than HSF-1 activation and transcription of HSP72 mRNA are responsible for this age-related impairment. stress proteins; cardioprotection; heart; heat shock protein AGING IS A MULTIFACTORIAL PROCESS resulting in damage to molecules, cells, and tissues. Eventually, this damage exceeds the capacity of the organism to adapt and/or repair the damage (49). Cells have evolved complex genetic systems to detect specific forms of stress and activate the expression of genes whose products increase the resistance of the cell to further stress and/or initiate the processes of tissue regeneration. Unfortunately, the expression of many of these genes is attenuated in aging (53, 63). As a consequence, cellular responsiveness to stress diminishes with advancing age.One of the best understood cellular responses to stress has been traditionally called the heat shock response. Cell stresses including heat stress and exercise result in preferential transcription and translation of heat shock proteins (HSPs). Overexpression of 72-kDa HSP (HSP72) is associated with protection of cardiomyocytes from a variety of stresses including myocardial ischemia-reperfusion (I/R) injury (33, 50). Heat stress-induced increases in myocardial HSP72 are associated with reduced myocardial damage after I/R in young animals (12, 13). Furthermore, we and others (14,23,24,43,45,56,60) have shown that endurance exercise elevates myocardial HSP72 and protects against myocardial I/R injury in young adult animals.Evidence indicates that mammalian aging is associated with decreased cellular expression of HSP72 in response to heat stress (6-8, 16, 21, 22, 26, 27, 38, 40-42). At present, the mechanism to explain the agerelated decline in myocardial HSP72 expr...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Age and attenuation of exercise-induced myocardial HSP72 accumulation

Demirel¹,

Hamilton²,

Shanely³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…In contrast to acute HS, the effects of chronic HS on gene expression and cellular metabolism have been studied only to a limited extent (Zhang et al 2002, Bhusari et al 2008. Acute and chronic HS pose two distinct challenges to animals.…”

Section: Introductionmentioning

confidence: 99%

Chronic heat stress up-regulates leptin and adiponectin secretion and expression and improves leptin, adiponectin and insulin sensitivity in mice

Morera¹,

Basiricò²,

Hosoda³

et al. 2012

Journal of Molecular Endocrinology

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Heat stress (HS) induces adaptive responses that are responsible for alterations of carbohydrate and lipid metabolism. This study aimed to evaluate the effects of chronic heat treatment on the expression and secretion of leptin and adiponectin, important regulators of energy homeostasis, food intake and insulin action. C57BL/6 mice were subdivided into three groups (24 mice each). The first group was kept under control conditions (C: 22G2 8C). The second group was exposed to HS (35G1 8C). The third group was kept under control conditions and was food restricted (FR). The HS group had higher rectal temperature than the C and FR groups and lower food intake than the C group. Hspa1 (Hspa1a) gene expression in adipose tissue, muscle and liver was higher under HS than FR and C. Heat treatment resulted in decreased blood glucose and non-esterified fatty acids; increased leptin, adiponectin and insulin secretion; and greater glucose disposal. Leptin, adiponectin, leptin and adiponectin receptors, insulin receptor substrate-1 and glucose transporter mRNAs were up-regulated in HS mice. This study provides evidence that HS improves leptin and adiponectin signalling in adipose tissue, muscle and liver. Heat stress was responsible for improving insulin sensitivity and glucose uptake in peripheral tissues, probably mediated by adipokines. Changes in the adipokine levels and sensitivity to them may be considered as an adaptive response to heat.

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“…During the aging process, the normal increase in the concentration of Hsp90 in response to thermal stress is attenuated in lymphocytes (4), liver cells (5), and mesenchymal stem cells (6). Diminished Hsp90 messenger RNA (mRNA) and protein synthesis following mitogen stimulation of lymphocytes with interleukin-2 (IL-2) has been measured in aged donors of T lymphocytes (7), and tissue from aged animals and blood from elderly humans show reduced production of stress proteins, including Hsp90, following thermal stress (4,8).…”

mentioning

confidence: 99%

“…Results from complementary DNA array experiments comparing liver cells from young and aged rats showed that altered gene expression in response to stress is indicative of decreased stress protein mRNA expression (5), and a 2-fold decrease in hsp90 mRNA expression has been detected in OA versus normal cartilage (9). Hsp90 is further implicated in altered homeostasis of aging articular cartilage through its requirement for proper telomerase assembly and function (10), particularly given the loss of telomere length with age in chondrocytes (11)(12)(13).…”

mentioning

confidence: 99%

Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes

Boehm¹,

Seth²,

Mayr³

et al. 2007

Arthritis & Rheumatism

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Objective. Many metabolic processes in chondrocytes thought to contribute to age-related changes in the extracellular matrix are influenced by known roles of Hsp90. Age-related decreases in the level of Hsp90 have been documented in numerous cell types and could contribute to cartilage degeneration. The aim of this study was to investigate the roles of age and Hsp90 in insulin-like growth factor 1 (IGF-1) and interleukin-1␤ (IL-1␤) signaling in chondrocytes.Methods. Levels of Hsp90 messenger RNA (mRNA) and protein, with respect to age, were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. The Hsp90 inhibitor geldanamycin (50 nM, 100 nM, or 500 nM) was used to assess age-related responses to Hsp90 with concurrent IGF-1 or IL-1␤ stimulation of chondrocytes. Quantitative real-time PCR was used to measure COL2A1 and matrix metalloproteinase 13 (MMP13) gene expression; Western blot analysis was performed to determine the phosphorylation status of p42/44 and Akt/protein kinase B.Results. The effects of Hsp90 inhibition with geldanamycin were concentration dependent. Inhibition of Hsp90 with 100 nM or 500 nM geldanamycin blocked IGF-1-induced cell proliferation, Akt and p42/44 activation, and COL2A1 expression. Basal and IL-1␤-induced up-regulation of MMP13 mRNA was blocked by all concentrations of geldanamycin tested. Gain-offunction assays with Hsp90 resulted in increased expression of MMP13 mRNA.Conclusion. These results suggest that Hsp90 is involved in opposing signaling pathways of cartilage homeostasis, and that catabolic responses are more sensitive to Hsp90 inhibition than are anabolic responses. Further studies are needed to determine the role of Hsp90 inhibition in osteoarthritis in order to assess its potential as a therapeutic target.

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Selected Contribution: Differential expression of stress-related genes with aging and hyperthermia

Cited by 30 publications

References 32 publications

Age and attenuation of exercise-induced myocardial HSP72 accumulation

Age and attenuation of exercise-induced myocardial HSP72 accumulation

Chronic heat stress up-regulates leptin and adiponectin secretion and expression and improves leptin, adiponectin and insulin sensitivity in mice

Hsp90 mediates insulin‐like growth factor 1 and interleukin‐1β signaling in an age‐dependent manner in equine articular chondrocytes

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