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Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis.

Tenorio-Laranga J, Coret-Ferrer F, Casanova-Estruch B, Burgal M, García-Horsman JA - J Neuroinflammation (2010)

Bottom Line: We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor.The lowered POP activity from plasma of MS patients could be rescued by reductants The decrease in circulating POP activity measured in MS is reverted by reductants.This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain.

ABSTRACT

Background: Multiple sclerosis (MS) is a complex, inflammatory and neurodegenerative disease of the central nervous system leading to long-term disability. Recent studies indicate a close association between inflammation and neurodegeneration in all lesions and disease stages of MS. Prolyl oligopeptidase (POP) is a proline-specific serine protease that cleaves several neuroactive peptides. This peptidase has been implicated in neurodegeneration, as well as in the modulation of the inflammatory response.

Methods: We examined plasma POP and the levels of an endogenous POP inhibitor from relapsing remitting MS patients and compared these with healthy controls, by monitoring the fluorescent changes due to standard fluorescently labelled substrate cleavage. We analysed the data in relationship to patient age and disease disability status.

Results: We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor. The POP activity was also correlated with patient age and disability status. The lowered POP activity from plasma of MS patients could be rescued by reductants

Conclusions: The decrease in circulating POP activity measured in MS is reverted by reductants. This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients. Plasma levels of POP activity as well as those of their endogenous inhibitor are suggested as biomarkers of inflammation and oxidative stress in MS.

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Effect of DTT on prolyl oligopeptidase levels in plasma from healthy and RR-MS patients. POP activity in plasma from healthy controls (white bar) and RR-MS patients (gray bar) after plasma pre-incubation in the absence, or presence (diagonal pattern), of DTT (5 mM). n = 10, p-values, **, 0.0024, ***, 0.0004.
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Figure 5: Effect of DTT on prolyl oligopeptidase levels in plasma from healthy and RR-MS patients. POP activity in plasma from healthy controls (white bar) and RR-MS patients (gray bar) after plasma pre-incubation in the absence, or presence (diagonal pattern), of DTT (5 mM). n = 10, p-values, **, 0.0024, ***, 0.0004.

Mentions: The increase of POP endogenous inhibitor was not sufficient to explain the substantial decrease in POP activity found in plasma from RR-MS patients. It has been reported that POP is sensitive to redox conditions and is inactivated by oxidants [35,36]. On the other hand, it has been demonstrated that reactive oxygen species (ROS) are substantially increased in MS [37-40]. Hence, we tested the effect of DTT (5 mM) on plasma POP activity. For this purpose, we repeated the POP assay for all samples but after a 5-min pre-incubation with 5 mM DTT. We found that DTT had no effect on POP activity in control samples. However, after pre-incubation with DTT, plasma from diseased patients showed increased POP activity comparable to control levels (p-value < 0.005) (Fig. 5).


Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis.

Tenorio-Laranga J, Coret-Ferrer F, Casanova-Estruch B, Burgal M, García-Horsman JA - J Neuroinflammation (2010)

Effect of DTT on prolyl oligopeptidase levels in plasma from healthy and RR-MS patients. POP activity in plasma from healthy controls (white bar) and RR-MS patients (gray bar) after plasma pre-incubation in the absence, or presence (diagonal pattern), of DTT (5 mM). n = 10, p-values, **, 0.0024, ***, 0.0004.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864237&req=5

Figure 5: Effect of DTT on prolyl oligopeptidase levels in plasma from healthy and RR-MS patients. POP activity in plasma from healthy controls (white bar) and RR-MS patients (gray bar) after plasma pre-incubation in the absence, or presence (diagonal pattern), of DTT (5 mM). n = 10, p-values, **, 0.0024, ***, 0.0004.
Mentions: The increase of POP endogenous inhibitor was not sufficient to explain the substantial decrease in POP activity found in plasma from RR-MS patients. It has been reported that POP is sensitive to redox conditions and is inactivated by oxidants [35,36]. On the other hand, it has been demonstrated that reactive oxygen species (ROS) are substantially increased in MS [37-40]. Hence, we tested the effect of DTT (5 mM) on plasma POP activity. For this purpose, we repeated the POP assay for all samples but after a 5-min pre-incubation with 5 mM DTT. We found that DTT had no effect on POP activity in control samples. However, after pre-incubation with DTT, plasma from diseased patients showed increased POP activity comparable to control levels (p-value < 0.005) (Fig. 5).

Bottom Line: We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor.The lowered POP activity from plasma of MS patients could be rescued by reductants The decrease in circulating POP activity measured in MS is reverted by reductants.This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurobiology, Centro de Investigación Príncipe Felipe, Valencia, Spain.

ABSTRACT

Background: Multiple sclerosis (MS) is a complex, inflammatory and neurodegenerative disease of the central nervous system leading to long-term disability. Recent studies indicate a close association between inflammation and neurodegeneration in all lesions and disease stages of MS. Prolyl oligopeptidase (POP) is a proline-specific serine protease that cleaves several neuroactive peptides. This peptidase has been implicated in neurodegeneration, as well as in the modulation of the inflammatory response.

Methods: We examined plasma POP and the levels of an endogenous POP inhibitor from relapsing remitting MS patients and compared these with healthy controls, by monitoring the fluorescent changes due to standard fluorescently labelled substrate cleavage. We analysed the data in relationship to patient age and disease disability status.

Results: We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor. The POP activity was also correlated with patient age and disability status. The lowered POP activity from plasma of MS patients could be rescued by reductants

Conclusions: The decrease in circulating POP activity measured in MS is reverted by reductants. This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients. Plasma levels of POP activity as well as those of their endogenous inhibitor are suggested as biomarkers of inflammation and oxidative stress in MS.

Show MeSH
Related in: MedlinePlus