+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Membrane phosphorylation protects the cardiac sarcoplasmic reticulum Ca(2+)-ATPase against chlorinated oxidants in vitro



Membrane phosphorylation protects the cardiac sarcoplasmic reticulum Ca(2+)-ATPase against chlorinated oxidants in vitro



Cardiovascular Research 36(1): 67-77



The calcium (Ca) pump of cardiac sarcoplasmic reticulum (SR) membranes is vulnerable to oxidation and hence likely to be damaged by chlorinated compounds, specifically hypochlorite (NaOCl) and monochloramine (NH2Cl), the most potent oxidants produced upon neutrophil activation. This could occur during prolonged ischemia or myocardial infarction when tissue levels of catecholamines are high. Phospholamban (PLN), the phosphorylatable regulator of the Ca pump, plays a central role in the effects of beta-adrenergic agonists on the heart. The purpose of this study was to investigate a possible role of PLN in determining the pump's sensitivity to NaOCl and NH2Cl. Ca-uptake and Ca(2+)-ATPase activities in purified phosphorylated and control canine cardiac microsomes, incubated at increasing concentrations of NaOCl or NH2Cl, were related to the extent of PLN phosphorylation by protein kinase A, which was quantitated by PhosphorImager analysis. Our data indicate that microsomal phosphorylation protects the Ca pump fully against 10 microM NaOCl or NH2Cl, which inhibit Ca-uptake by 21-41% when assayed at 25 or 37 degrees C and saturating Ca2+ in unphosphorylated microsomes, and protects partially at higher oxidant concentrations. The protective effect of protein kinase A on Ca-uptake is proportional to the amount of phosphorylated PLN. No comparable protection against similar oxidative damage of the Ca pump is observed when light fast skeletal muscle microsomes, which lack PLN, are incubated under conditions favorable for phosphorylation nor when PLN's inhibition of the cardiac Ca pump is relieved by proteolytic cleavage of its cytoplasmic domain. Our findings contribute toward an understanding of possible endogenous protective mechanisms that may promote calcium homeostasis in myocardial cells in inflammatory states associated with neutrophil activation and may suggest an approach toward development of protective strategies against oxidative damage in the heart.

(PDF emailed within 1 workday: $29.90)

Accession: 046661565

Download citation: RISBibTeXText

PMID: 9415274


Related references

Apelin protects sarcoplasmic reticulum function and cardiac performance in ischaemia-reperfusion by attenuating oxidation of sarcoplasmic reticulum Ca2+-ATPase and ryanodine receptor. Cardiovascular Research 100(1): 114-124, 2014

Cyclic amp stimulation of membrane phosphorylation and calcium ion activated magnesium ion dependent atpase ec 3.6.1.15 in cardiac sarcoplasmic reticulum. Biochimica et Biophysica Acta 461(3): 441-459, 1977

In vitro effects of palmityl carnitine on cardiac plasma membrane sodium potassium atpase and sarcoplasmic reticulum calcium atpase and calcium transport. Journal of Biological Chemistry 254(24): 12404-12410, 1979

Enhanced phosphorylation of phospholamban and downregulation of sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA 2) in cardiac sarcoplasmic reticulum from rabbits with heart failure. Cardiovascular Research 41(1): 135-146, 1999

GroEL protects the sarcoplasmic reticulum Ca -dependent ATPase from inactivation in vitro. Iubmb Life 47(4): 631-638, 1999

GroEL protects the sarcoplasmic reticulum Ca(++)-dependent ATPase from inactivation in vitro. Biochemistry and Molecular Biology International 47(4): 631-638, 1999

Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity. Circulation Research 89(2): 160-167, 2001

Effect of calmodulin of calcium uptake atpase and phosphorylation of cardiac sarcoplasmic reticulum. Naunyn Schmiedeberg'S Archives Of Pharmacologyuppl: R37, 1982

Phosphorylation of the calcium transport atpase of cardiac sarcoplasmic reticulum by ortho phosphate. European Journal of Biochemistry 77(3): 611-620, 1977

Alteration of acylphosphate formation of cardiac sarcoplasmic reticulum ATPase by calmodulin-dependent phosphorylation. Zeitschrift für Naturforschung. Section C, Biosciences 39(3-4): 289-292, 1984

Rearrangement of domain elements of the Ca-ATPase in cardiac sarcoplasmic reticulum membranes upon phospholamban phosphorylation. Biochemistry 38(25): 8150-8158, 1999

Phosphorylation of the calcium transport atpase of cardiac sarcoplasmic reticulum by phosphorus 32 ortho phosphate. Naunyn-Schmiedeberg's Archives of Pharmacology 293(SUPPL): R23, 1976

Effect of phospholamban phosphorylation on calcium dependent atpase of solubilized cardiac sarcoplasmic reticulum. Japanese Circulation Journal 47(8): 1021, 1983

Phospho lamban phosphorylation protects cardiac sarcoplasmic reticulum from the inhibitory effects of unsaturated fatty acids. Clinical Research 30(2): 201A, 1982

Sarcoplasmic reticulum part 15 dissociation of the membrane atpase enzyme of sarcoplasmic reticulum into subunits by ultrasonic treatment. Archives of Biochemistry & Biophysics 151(2): 558-564, 1972