Increased Activity of Cell Surface Peptidases in HeLa Cells Undergoing UV-Induced Apoptosis Is Not Mediated by Caspase 3

We have previously shown that in HeLa cells treated with a variety of agents there is an increase in cell surface peptidase (CSP) activity in those cells undergoing apoptosis. The increase in CSP activity observed in UVB-irradiated cells undergoing apoptosis was unaffected when the cultures were treated with the aminopeptidase inhibitor bestatin, and matrix metalloprotease inhibitor BB3103, but greatly enhanced when treated with the caspase 3 inhibitor-DEVD, and reduced in the presence of the poly(ADP-ribose) polymerase (PARP) inhibitor-3-aminobenzamide (3AB). Neither 3AB nor DEVD had an effect on the gross morphology of the apoptotic cells observed under electron microscopy, nor did they have an effect on phosphatidylserine eversion on the cell membrane, or that of PARP cleavage. All the agents except for DEVD had no effect on the level of caspase 3 activity in the cells. The results suggest that other caspases may cleave PARP in these cells. Both 3AB and DEVD treatment reduced the level of actin cleavage seen in the apoptotic cells. The increase in CSP activity observed in cells undergoing UVB-induced apoptosis appears to involve PARP but not caspase 3

Linear regression coefficient (b), 95% CI and p-value of baseline predictors of the RoR and BP_Power as natural log (ln) from a univariate and multivariate analysis of 409 subjects.

<p>Linear regression coefficient (b), 95% CI and p-value of baseline predictors of the RoR and BP_Power as natural log (ln) from a univariate and multivariate analysis of 409 subjects.</p

Clinical characteristics of subject groups.

<p>Values are Mean +/- SD, <i>P</i>1 is the probability for the comparison between females and males. <i>P</i>2 is the probability between baseline and follow up.</p

Correlations between natural log morning rate of rise (RoR) in mean arterial pressure (MAP) (left panels) and power (right panels) and plasma levels of cholesterol (top), low density lipoprotein (LDL, middle) and high density lipoprotein (HDL) from subjec

<p>Thick line represents least squares regression lines and thin lines are 99% confidence limits. r is the correlation co-efficient and P is the probability.</p

Correlations between post awake 2(MAP) (left panels) and post awake 2 hours minus pre awake 2 hours (right panels) and plasma levels of cholesterol (top), low density lipoprotein (LDL, middle) and high density lipoprotein (HDL) from subjects (n = 307).

<p>Thick line represents least squares regression lines and thin lines are 99% confidence limits. r is the correlation co-efficient and P is the probability.</p

Correlations between natural log morning rate of rise (RoR) in mean arterial pressure (MAP) (left panels) and power (right panels) and body mass index (BMI) and age from subjects (n = 409).

<p>Thick line represents least squares regression lines and thin lines are 99% confidence limits. r is the correlation co-efficient and P is the probability.</p

Linear regression coefficient (b), 95% CI and p-value of baseline predictors of the change in natural log (ln) RoR and BP_power between first follow-up and baseline visits from a univariate and multivariate ANCOVA analysis of recordings from 213

#<p>Also adjusted for baseline ln ROR and time between visits,</p>∧<p>Also adjusted for baseline ln BP_power and time between visits.</p

Predictors of mean arterial pressure morning rate of rise and power function in subjects undergoing ambulatory blood pressure recording

Background: We determined clinical predictors of the rate of rise (RoR) in blood pressure in the morning as well as a novel measure of the power of the BP surge (BPpower) derived from ambulatory blood pressure recordings. Methods: BPpower and RoR were calculated from 409 ambulatory blood pressure (ABP) recordings from subjects attending a cardiovascular risk clinic. Anthropometric data, blood biochemistry, and history were recorded. The 409 subjects were 20-82 years old (average 57, SD = 13), 46% male, 9% with hypertension but not on medication and 34% on antihypertensive medication. Results: Average RoR was 11.1 mmHg/hour (SD = 8) and BPpower was 273 mmHg2/hour (SD = 235). Only cholesterol, low density lipoprotein and body mass index (BMI) were associated with higher BPpower and RoR (P&lt;0.05) from 25 variables assessed. BPpower was lower in those taking beta-blockers or diuretics. Multivariate analysis identified that only BMI was associated with RoR (4.2% increase/unit BMI, P = 0.020) while cholesterol was the only remaining associated variable with BPpower (17.5% increase/mmol/L cholesterol, P = 0.047). A follow up of 213 subjects with repeated ABP after an average 1.8 years identified that baseline cholesterol was the only predictor for an increasing RoR and BPpower (P&lt;0.05). 37 patients who commenced statin subsequently had lower BPpower whereas 90 age and weight matched controls had similar BPpower on follow-up. Conclusions: Cholesterol is an independent predictor of a greater and more rapid rise in morning BP as well as of further increases over several years. Reduction of cholesterol with statin therapy is very effective in reducing the morning blood pressure surge. © 2014 Head et al