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Targeting Heat Shock Proteins Mitigates Ventilator Induced Diaphragm Muscle Dysfunction in an Age-Dependent Manner

View Article: PubMed Central - PubMed

ABSTRACT

Intensive care unit (ICU) patients are often overtly subjected to mechanical ventilation and immobilization, which leads to impaired limb and respiratory muscle function. The latter, termed ventilator-induced diaphragm dysfunction (VIDD) has recently been related to compromised heat shock protein (Hsp) activation. The administration of a pharmacological drug BGP-15 acting as a Hsp chaperone co-inducer has been found to partially alleviate VIDD in young rats. Considering that the mean age in the ICU is increasing, we aimed to explore whether the beneficial functional effects are also present in old rats. For that, we exposed young (7–8 months) and old (28–32 months) rats to 5-day controlled mechanical ventilation and immobilization with or without systemic BGP-15 administration. We then dissected diaphragm muscles, membrane–permeabilized bundles and evaluated the contractile function at single fiber level. Results confirmed that administration of BGP-15 restored the force-generating capacity of isolated muscle cells from young rats in conjunction with an increased expression of Hsp72. On the other hand, our results highlighted that old rats did not positively respond to the BGP-15 treatment. Therefore, it is of crucial importance to comprehend in more depth the effect of VIDD on diaphragm function and ascertain any further age-related differences.

No MeSH data available.


Western blot analyses of the Hsp72 protein expression normalized to actin contents in the diaphragm in control animals (individual rats: young n = 4 and old emphn = 2) compared with the age-matched animals exposed to CMV for 5 days with (individual rats: young n = 3 and old n = 2) and without BGP-15 (individual rats: young n = 3 and old n = 3). (Black bars, young; white bars, old). Values are means + SEM. Significance level, *p < 0.05.
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Figure 5: Western blot analyses of the Hsp72 protein expression normalized to actin contents in the diaphragm in control animals (individual rats: young n = 4 and old emphn = 2) compared with the age-matched animals exposed to CMV for 5 days with (individual rats: young n = 3 and old n = 2) and without BGP-15 (individual rats: young n = 3 and old n = 3). (Black bars, young; white bars, old). Values are means + SEM. Significance level, *p < 0.05.

Mentions: Hsp72 protein levels did not differ between young and old animals in the control group or after 5 days CMV. However, the increase (p < 0.05) in Hsp72 levels observed in response to 5 days BGP-15 administration in mechanically ventilated rats was restricted to the young animals (Figure 5).


Targeting Heat Shock Proteins Mitigates Ventilator Induced Diaphragm Muscle Dysfunction in an Age-Dependent Manner
Western blot analyses of the Hsp72 protein expression normalized to actin contents in the diaphragm in control animals (individual rats: young n = 4 and old emphn = 2) compared with the age-matched animals exposed to CMV for 5 days with (individual rats: young n = 3 and old n = 2) and without BGP-15 (individual rats: young n = 3 and old n = 3). (Black bars, young; white bars, old). Values are means + SEM. Significance level, *p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037190&req=5

Figure 5: Western blot analyses of the Hsp72 protein expression normalized to actin contents in the diaphragm in control animals (individual rats: young n = 4 and old emphn = 2) compared with the age-matched animals exposed to CMV for 5 days with (individual rats: young n = 3 and old n = 2) and without BGP-15 (individual rats: young n = 3 and old n = 3). (Black bars, young; white bars, old). Values are means + SEM. Significance level, *p < 0.05.
Mentions: Hsp72 protein levels did not differ between young and old animals in the control group or after 5 days CMV. However, the increase (p < 0.05) in Hsp72 levels observed in response to 5 days BGP-15 administration in mechanically ventilated rats was restricted to the young animals (Figure 5).

View Article: PubMed Central - PubMed

ABSTRACT

Intensive care unit (ICU) patients are often overtly subjected to mechanical ventilation and immobilization, which leads to impaired limb and respiratory muscle function. The latter, termed ventilator-induced diaphragm dysfunction (VIDD) has recently been related to compromised heat shock protein (Hsp) activation. The administration of a pharmacological drug BGP-15 acting as a Hsp chaperone co-inducer has been found to partially alleviate VIDD in young rats. Considering that the mean age in the ICU is increasing, we aimed to explore whether the beneficial functional effects are also present in old rats. For that, we exposed young (7&ndash;8 months) and old (28&ndash;32 months) rats to 5-day controlled mechanical ventilation and immobilization with or without systemic BGP-15 administration. We then dissected diaphragm muscles, membrane&ndash;permeabilized bundles and evaluated the contractile function at single fiber level. Results confirmed that administration of BGP-15 restored the force-generating capacity of isolated muscle cells from young rats in conjunction with an increased expression of Hsp72. On the other hand, our results highlighted that old rats did not positively respond to the BGP-15 treatment. Therefore, it is of crucial importance to comprehend in more depth the effect of VIDD on diaphragm function and ascertain any further age-related differences.

No MeSH data available.