Cpx System Research Articles

Presence of the Cpx system in bacteria.

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The CpxRA signal transduction system of Escherichia coli: growth-related autoactivation and control of unanticipated target operons.

In Escherichia coli, the CpxRA two-component signal transduction system senses and responds to aggregated and misfolded proteins in the bacterial envelope. We show that CpxR-P (the phosphorylated form of the cognate response regulator) activates cpxRA expression in conjunction with RpoS, suggesting an involvement of the Cpx system in stationary-phase survival. Engagement of the CpxRA system in functions beyond protein management is indicated by several putative targets identified after a genomic screening for the CpxR-P recognition consensus sequence. Direct negative control of the newly identified targets motABcheAW (specifying motility and chemotaxis) and tsr (encoding the serine chemoreceptor) by CpxR-P was shown by electrophoretic mobility shift analysis and Northern hybridization. The results suggest that the CpxRA system plays a core role in an extensive stress response network in which the coordination of protein turnover and energy conservation may be the unifying element.

ESTIMATION OF OXYGEN CONSUMPTION IN CARDIAC PATIENTS UNDERGOING RAMP TREADMILL EXERCISE

1206 Errors in estimating peak oxygen consumption (VO2peak) using ACSM formulae in clinical populations have been well described. The aim of this investigation was to develop an accurate prediction equation for cardiac patients undergoing RAMP treadmill exercise. One hundred and one subjects with heart disease were tested to symptom-limited peak exertion following an individualized RAMP protocol where a speed, target test time, and target MET level were chosen prior to each test. Oxygen consumption was measured with a Medical Graphics CPX system. The following equation (WAKE) was developed using speed and grade as the predictor variables during treadmill walking: VO2peak (ml·kg−1·min−1) = [4.242 × speed (mph)] + [0.604 × grade (%)] + 2.704 (R = 0.854, R2 = 0.730, SEE = 2.62 ml·kg−1·min−1). The accuracy of the WAKE equation, as well as several other prediction equations (ACSM, FAST, and FOSTER), in predicting VO2peak during RAMP treadmill testing was compared to measured VO2peak (MEAS) (mean = 25.6 ± 0.7 ml·kg−1·min−1) in an independent sample of cardiac patients (n=129) from our lab. MEAS was then regressed against the estimated VO2peak for each prediction equation. (Table)TableResults show that the mean estimated VO2peak from each equation was significantly different from MEAS. However, all estimated values were highly correlated with MEAS. The WAKE equation appeared to yield the most accurate estimation of VO2peak in this population. Both the FAST and FOSTER equations resulted in an improved estimation of VO2peak compared to ACSM.

ESTIMATION OF OXYGEN CONSUMPTION IN CARDIAC PATIENTS UNDERGOING RAMP TREADMILL TESTING

430 Errors in estimating peak oxygen consumption (VO2peak) using ACSM formulae in clinical populations have been well reported. Several researchers have attempted to correct these errors by developing formulae that are more accurate and, in some cases, population specific. However, research has shown that these equations do not accurately predict VO2 in cardiac patients undergoing RAMP treadmill testing. As the use of RAMP treadmill protocols increases, estimating VO2 when using this protocol becomes important for clinicians. The intent of this investigation was to develop a prediction equation for cardiac patients undergoing RAMP treadmill testing. One hundred and five subjects with heart disease were tested to symptomlimited peak exertion following an individualized RAMP protocol where a speed, target test time, and target MET level were chosen prior to each test. Oxygen consumption was measured with a Medical Graphics CPX system. The following equation (RAMP) was developed using speed and grade as the predictor variables during treadmill walking: VO2(ml·kg-1·min-1) =[3.6393 × speed(mph)] + [0.7753 × grade(%)] + 2.2025(ml·kg-1·min-1), (R2=0.83, SEE=5.31). The accuracy of the RAMP equation, as well as several other prediction equations (ACSM, FAST, and FOSTER), in predicting VO2peak during RAMP treadmill testing was compared to measured VO2peak (MEAS) in an independent sample of cardiac patients (n=129) from our lab. Data were analyzed using a repeated measures ANOVA. VO2, in ml·kg-1·min-1, are presented as mean±SEM(*p<0.05 as compared to MEAS). TableTableResults show that all prediction equations differ significantly from measured VO2peak. These differences, coupled with a large standard error of the estimate for the RAMP equation, suggest that there is significant error in estimating VO2peak in cardiac patients undergoing RAMP treadmill testing, thus necessitating direct measurement of VO2.

The sigma(E) and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli.

In Escherichia coli, the heat shock-inducible sigma-factor sigma(E) and the Cpx two-component signal transduction system are both attuned to extracytoplasmic stimuli. For example, sigma(E) activity rises in response to the overproduction of various outer-membrane proteins. Similarly, the activity of the Cpx signal transduction pathway, which consists of an inner-membrane sensor (CpxA) and a cognate response regulator (CpxR), is stimulated by overproduction of the outer-membrane lipoprotein, NlpE. In response to these extracytoplasmic stimuli, sigma(E) and CpxA/CpxR stimulate the transcription of degP, which encodes a periplasmic protease. This suggests that CpxA/CpxR and sigma(E) both mediate protein turnover within the bacterial envelope. Here, we show that CpxA/CpxR and sigma(E) also control the synthesis of periplasmic enzymes that can facilitate protein-folding reactions. Specifically, sigma(E) controls transcription of fkpA, which specifies a periplasmic peptidyl-prolyl cis/trans isomerase. Similarly, the Cpx system controls transcription of the dsbA locus, which encodes a periplasmic enzyme required for efficient disulfide bond formation in several extracytoplasmic proteins. Taken together, these results indicate that sigma(E) and CpxA/CpxR are involved in regulating both protein-turnover and protein-folding activities within the bacterial envelope.

COMPARISON OF PEAK OXYGEN CONSUMPTION AND VENTILATORY THRESHOLD IN ELDERLY SUBJECTS WITH NORMAL VENTRICULAR FUNCTION, SYSTOLIC DYSFUNCTION, OR DIASTOLIC DYSFUNCTION 441

Peak oxygen consumption and ventilatory threshold (VT) have prognostic and functional implications in patients with left ventricular systolic dysfunction(SD). Although younger patients with SD have been well studied, there is little data on elderly patients with SD or on patients with primary diastolic dysfunction (DD), a common cause of congestive heart failure (CHF) in the elderly. Consequently, we compared 114 consecutive elderly patients (mean age=70 yrs) with stable (NYHA class II - III) CHF due to SD (n=55) or DD(n=59) at baseline of a NIH sponsored trial to 31 age-matched normal subjects(NL). All subjects underwent screening echocardiograms to exclude significant ischemia and valvular disease and for measurement of resting left ventricular ejection fraction (LVEF). Subjects were tested to symptom-limited maximal levels on a calibrated bicycle ergometer while expired gases were collected breath-by-breath with a Medical Graphics CPX system. Peak oxygen consumption values were the highest value obtained during a 15 sec. interval and VT was determined by a blinded observer using the “v-slope” method and traditional ventilatory and gas exchange variables. VT was identifiable in 100% of NL and 85% of CHF patients. Data are presented as mean± SD.Table Conclusion: Peak oxygen consumption and ventilatory threshold in elderly patients with CHF due to DD are severely reduced compared to age-matched NL and are similar to what is observed in patients with SD.