title: Plasminogen activator activity is decreased in rat gingiva during diabetes.
abstract: Diabetes produces extensive alterations of collagen metabolism including enhanced gingival collagenase activity. However, the mechanism for this enhanced enzyme activity is unclear. Collagenase is secreted from cells in a latent form and plasmin has been proposed as an important in vivo activator of procollagenase. Plasmin is converted from its precursor, plasminogen, by the proteolytic action of a serine proteinase, plasminogen activator (PA). The current study was therefore undertaken to determine the effect of diabetes on gingival PA activity in the rat. Since doxycycline is a potent collagenase inhibitor, the effect of doxycycline on gingival PA activity was also investigated. Eighteen male, Sprague-Dawley rats were made diabetic by streptozotocin injection (7 mg/100 g). Control rats (N = 8) were sham-treated. Doxycycline (5 mg/day/rat) was administered to 9 of the 18 diabetic rats by gavage on a daily basis. The other 9 diabetic rats were administered with saline. After 3 weeks, blood and gingival tissue were collected from each rat for the determination of glucose level and gingival PA activity. The tissues were then minced and extracted with 5 mM sodium phosphate containing 1% Triton X-100. PA assay was performed using chromatogenic substrate to determine PA activity in the extracts. Gingival PA activity in the diabetic rats was significantly reduced compared to the control (13.5 +/- 1.6 vs. 36.0 +/- 3.3 microunits/100 micrograms protein, P < 0.01). Doxycycline administration to diabetic rats had no effect on the already reduced gingival PA activity (10.4 +/- 3.5 in doxycycline-treated rats vs. 13.5 +/- 1.6 mu units/100 micrograms protein in untreated diabetic rats). PA activities in gingival tissues from the diabetic, nondiabetic control and doxycycline-treated diabetic groups were also demonstrated on zymographs as lytic bands. Regarding the well-known fact that gingival collagenase activity is enhanced during diabetes, our results did not support the notion that this biochemical alteration is attributed to increased activation of procollagenase by PA.
authors.affiliation: Department of Periodontics, New Jersey Dental School, Newark, USA.
authors.forename: K
authors.initials: K
authors.lastname: Chang
authors.forename: A S
authors.initials: AS
authors.lastname: Rani
authors.forename: K
authors.initials: K
authors.lastname: Chang
authors.forename: S
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D005881:Gingiva / Q000378:metabolism*; D005947:Glucose / Q000032:analysis; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010960:Plasminogen Activators / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000097:blood / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000097:blood / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D061965:Matrix Metalloproteinase Inhibitors; D013311:Streptozocin; D003094:Collagen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; C022440:procollagenase; D005947:Glucose; D004318:Doxycycline