Biomedical subjects

Xiaoling Su

Publications and source records attributed to Xiaoling Su.

5 recordsLinked to original sources

PubMed2004

Diabetes decreases rabbit bladder smooth muscle contraction while increasing levels of myosin light chain phosphorylation.

The effect of diabetes mellitus on the regulation of urinary bladder smooth muscle contraction was studied. Diabetes was induced in the rabbit by alloxan injection followed by 16 wk of housing. The bladder was harvested and strips of wall devoid of both mucosa and serosa were examined. Intact strips of bladder smooth muscle from diabetic animals produced less stress in response to membrane depolarization than muscle from control animals; sensitivity to KCl was not changed. Carbachol responses were similar in muscle strips from the two animal groups. Basal myosin light chain (MLC) phosphorylation levels were significantly elevated in response to most stimuli in muscle strips from diabetic animals, although levels of stress were either unchanged or lower. alpha-Toxin-permeabilized strips that allow for control of the intracellular environment while maintaining excitation-contraction coupling showed increased levels of MLC phosphorylation but decreased sensitivity to activator Ca2+ in smooth muscle from diabetic animals. MLC phosphatase contents were similar in smooth muscle from the two animal groups; however, MLC phosphatase activity was greater in muscle from control compared with diabetic animals. These results suggest that diabetes mellitus uncouples basal MLC phosphorylation from force in the bladder smooth muscle cell.

Animals↗

PubMed2004

Caldesmon phosphorylation is catalyzed by two kinases in permeabilized and intact vascular smooth muscle.

Smooth muscle contraction is initiated by myosin light chain (MLC) phosphorylation catalyzed by the Ca(2+) dependent MLC kinase. However, many aspects of smooth muscle contraction cannot be accounted for by MLC phosphorylation. One hypothesis that has received experimental support involves the thin filament protein caldesmon. Caldesmon inhibits myosin ATPase activity; phosphorylation of caldesmon relieves this inhibitory effect. The primary candidates for catalysis of caldesmon phosphorylation are the p42/p44 ERK MAP kinases. However, we and others have shown that inhibition of the ERK MAP kinases has no effect on many smooth muscles. The goal of this study was to determine if evidence for a second endogenous caldesmon kinase may be obtained. We used Triton X-100 skinned and intact tissues of the swine carotid artery to address this goal. Caldesmon phosphorylation was evident in resting and Ca(2+) stimulated Triton X-100 skinned fibers. Ca(2+)-dependent caldesmon phosphorylation was partially sensitive to the ERK MAP kinase inhibitor PD98059, whereas all caldesmon phosphorylation was sensitive to the general kinase inhibitor, staurosporine. Histamine increased caldesmon phosphorylation levels in intact swine carotid artery, which was sensitive to both PD98059 and staurosporine. Histamine increased ERK MAP kinase activity, which was reversed by PD98059, staurosporine, and EGTA. Histamine-induced contractions were inhibited by staurosporine but not by PD98059. We interpret these results to suggest that although ERK MAP kinases catalyze caldesmon phosphorylation, a second staurosporine sensitive kinase is also important in caldesmon phosphorylation and it is this pathway that may be more important in contractile regulation.

Adenosine Triphosphate↗

PubMed2003

Phosphatidylinositol 3-kinase modulates vascular smooth muscle contraction by calcium and myosin light chain phosphorylation-independent and -dependent pathways.

Regulation of smooth muscle contraction involves a number of signaling mechanisms that include both kinase and phosphatase reactions. The goal of the present study was to determine the role of one such kinase, phosphatidylinositol (PI)3-kinase, in vascular smooth muscle excitation-contraction coupling. Using intact medial strips of the swine carotid artery, we found that inhibition of PI3-kinase by LY-294002 resulted in a concentration-dependent decrease in the contractile response to both agonist stimulation and membrane depolarization-dependent contractions and a decrease in Ca(2+)-dependent myosin light chain (MLC) phosphorylation, the primary step in the initiation of smooth muscle contraction. Inhibition of PI3-kinase also depressed phorbol dibutyrate-induced contractions, which are not dependent on either Ca(2+) or MLC phosphorylation but are dependent on protein kinase C. To determine the Ca(2+)-dependent site of action of PI3-kinase, we determined the effect of several inhibitors of calcium metabolism on LY-294002-dependent inhibition of contraction. These inhibitors included nifedipine, SK&F-96365, and caffeine. Only SK&F-96365 blocked the LY-294002-dependent inhibition of contraction. Interestingly, all compounds blocked the LY-294002-dependent inhibition of MLC phosphorylation. Our results suggest that activation of PI3-kinase is involved in a Ca(2+)- and MLC phosphorylation-independent pathway for contraction likely to involve protein kinase C. In addition, our results also suggest that activation of PI3-kinase is involved in Ca(2+)-dependent signaling at the level of receptor-operated calcium channels.

Animals↗

PubMed2003

Sensitivity of rabbit aorta and mesenteric artery to norepinephrine: role of tyrosine kinases.

We tested the hypothesis that the differential sensitivity of rabbit aorta and mesenteric artery to norepinephrine is due to tyrosine kinase activity. The EC50 of aorta to norepinephrine was 6.5 times more sensitive than that in mesenteric artery. Basal myosin light chain phosphorylation was significantly greater in aorta as compared to mesenteric artery. Vanadate increased norepinephrine sensitivity significantly more in mesenteric artery than aorta, whereas genistein had the opposite effect. Basal phosphotyrosine levels were significantly higher in aorta than in mesenteric artery, the percentage increase in total tyrosine phosphorylated protein was significantly higher in mesenteric artery. These results suggest that the higher basal phosphotyrosine levels in the aorta may be responsible for the higher basal level of myosin light chain phosphorylation and this may be the basis for the higher sensitivity of the aorta to norepinephrine when compared with the mesenteric artery.

Animals↗

PubMed2002

Effect of partial outlet obstruction on rabbit urinary bladder smooth muscle function.

Bladder outlet obstruction secondary to benign prostate hyperplasia is associated with many cellular changes. This study was designed to determine whether these changes involve the contractile apparatus. Bladder smooth muscles from rabbits subjected to partial outlet obstruction for 2 wk were mounted for isometric force, isotonic shortening velocity, and myosin light chain (MLC) phosphorylation levels. Muscle strips from obstructed bladders exhibited spontaneous phasic activity; muscle strips from control bladders did not. Muscle strips from obstructed bladders exhibited increased sensitivity and higher levels of stress in response to the cumulative addition of KCl or carbachol compared with control. During noncumulative addition of KCl or carbachol, no differences in sensitivity were noted. Muscle strips from obstructed bladders had elevated basal MLC phosphorylation levels and stimulation produced small increases in MLC phosphorylation compared with control. V(max) during KCl stimulation of muscle strips from obstructed bladders was 10-fold lower than control. Our results suggest that bladder outlet obstruction produces a muscle cell that develops higher levels of force but with greatly reduced cross bridge cycling rates.

Animals↗