19 research outputs found
Localization of thrombospondin-l and its cysteine-serine-valine-threonine-cysteine-glycine receptor in colonic anastomotic healing tissue
Thrombospondin-l (TSP-1) is a matrix
protein implicated in mechanisms of wound healing.
TSP-1 contains the sequence cysteine-serine-valinethreonine-
cysteine-glycine (CSVTCG) that has been
shown to function primarily as a cell adhesion domain.
Our laboratory has isolated a novel receptor specific for
the CSVTCG adhesive domain of TSP-1. Immunohistochemical
staining techniques and computerized image
analysis were used to identify and quantitate TSP-1 and
its CSVTCG receptor in surgically created colon
anastomotic wounds. Histopathologic and quantitative
examination demonstrated increased expression of TSP-
1 and its CSVTCG receptor in areas of wound healing.
These findings suggest a role for TSP-1 and its
CSVTCG receptor in wound healing. The control of
expression and activity of these molecules may
eventually be the basis for the development of wound
healing agents that could significantly reduce the
morbidity from surgical intervention
The localization of thrombospondin-1 (TSP-1), cysteine-serine-valine-threoninecysteine- glycine (CSVTCG) TSP receptor, and matrix metalloproteinase-9 (MMP-9) in colorectal cancer
Thrombospondin-1 (TSP-1) is a 450 kDa
matrix bound glycoprotein involved in tumor invasion,
metastasis, and angiogenesis. One of the receptors
involved in TSP-1 mediated tumor cell adhesion and
metastasis is the cysteine-serine-valine-threoninecysteine-
glycine (CSVTCG) receptor. One mechanism
of TSP-1 in promoting tumor cell metastasis involves the
up-regulation of matrix metalloproteinase-9 (MMP-9)
expression, specifically through the CSVTCG TSP-1
receptor. TSP-1 and its CSVTCG receptor has been
implicated in tumor progression in a variety of cancers
including breast adenocarcinomas, head and neck
squamous cell carcinomas, and pancreatic carcinomas.
In this study, we examined 99 cases of colorectal
cancer by immunohistochemical analysis to investigate
1) the localization of TSP-1 and CSVTCG TSP-1
receptor, 2) the relationship with MMP-9, and 3) the
correlation of expression with clinical staging.
Strong expression of TSP-1 was observed in the
submucosa or the serosa adjacent to the tumor. Positive
staining for CSVTCG TSP-1 receptor was observed in
tumor cells and microvessels. MMP-9 was also
expressed in tumor cells. In addition, staining intensity
of CSVTCG TSP-1 receptor was higher in poorly
differentiated adenocarcinoma than well or moderately
differentiated adenocarcinoma. Tumors in which
inflammatory cells stained strongly for CSVTCG TSP-1
receptor correlated with decreased incidence of distant metastasis and angiogenesis.
These data were consistent with our previous studies
for breast, pancreatic, and head and neck carcinoma.
They suggest an important role for TSP-1 and CSVTCG
TSP-1 receptor in tumor progression in colorectal
cancer
Histopathology and clinical assessment correlate with the cysteine-serine-valinethreonine- cysteine-glycine (CSVTCG) receptor of thrombospondin-1 in breast tumors
Thrombospondin-1 (TSP-1) is a matrix
protein implicated in mechanisms of tumor metastasis.
TSP-1 has a characteristic Cysteine-Serine-Valine-
Threonine-Cysteine-Glycine (CSVTCG) sequence that
functions as a tumor cell adhesion domain. Our
laboratory has isolated a novel CSVTCG specific tumor
cell receptor. Immunohistochemical staining techniques
and computerized image analysis were used to identify
and quantitate the CSVTCG receptor of TSP-1 in a wide
spectrum of human archiva1 breast tumors. Histopathologic
and quantitative examination was correlated
with clinical findings two years post operation.
Increasing amounts of CSVTCG receptor correlated
positively with worsening histopathologic and clinical
findings. These findings suggest a role for the TSP-1
CSVTCG receptor in breast tumor progression. This
receptor may have utility for the diagnosis, staging, and
treatrnent of this common and deadly disease
Nitridergic platelet pathway activation by hementerin, a metalloprotease from the leech Haementeria depressa
Hementerin (HT) is an 80 kDa fibrino(geno)lytic metalloprotease, purified from saliva of the leech Haementeria depressa. in the present report, the effect of HT on several functional parameters of human platelets was assessed. HT inhibited platelet aggregation and ATP release induced by different agonists such as ADP, adrenaline, collagen, thrombin, and arachidonic acid. HT did neither modify the expression of platelet glycoproteins (Ib, IIbIIIa, IaIIa, IV) nor intraplatelet fibrinogen levels, whereas it markedly decreased CD62P and CD63 levels after the stimulation with thrombin. HT significantly increased thrombininduced platelet Ca2+ intracellular levels, cGMP content and nitric oxide synthase (NOS) activity. the effect of HT on platelet aggregation was reversed by two NOS inhibitors, N-omega-Nitro-L-arginine methyl ester and 2 N-G-Nitro-L-arginine. in summary, these results indicate that HT is an effective inhibitor of human platelet aggregation, presumably through activation of the platelets nitridergic pathway.Inst Butantan, Lab Bioquim & Biofis, BR-05503900 São Paulo, BrazilAcad Nacl Med Buenos Aires, IIHEMA, Buenos Aires, DF, ArgentinaUniv Buenos Aires, Fac Med, Dept Bioquim Humana, Buenos Aires, DF, ArgentinaUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim, São Paulo, BrazilWeb of Scienc
Kinesin as an Electrostatic Machine
Kinesin and related motor proteins utilize ATP fuel to propel themselves along the external surface of microtubules in a processive and directional fashion. We show that the observed step-like motion is possible through time-varying charge distributions furnished by the ATP hydrolysis cycle while the static charge configuration on the microtubule provides the guide for motion. Thus, while the chemical hydrolysis energy induces appropriate local conformational changes, the motor translational energy is fundamentally electrostatic. Numerical simulations of the mechanical equations of motion show that processivity and directionality are direct consequences of the ATP-dependent electrostatic interaction between the different charge distributions of kinesin and the microtubule