Characterization of Substance P processing in mouse spinal cord S9 fractions using high-resolution Quadrupole-Orbitrap mass spectrometry

Saidi, Mouna; Kamali, Soufiane; Beaudry, Francis

doi:10.1016/j.npep.2016.06.002

Cited by 15 publications

(7 citation statements)

References 37 publications

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“…Similar to other biological macromolecular drugs, in vivo SP is very susceptible to chemical and enzymatic degradation and it has a very short half-life, from seconds to minutes [ 13 , 22 , 23 ]. Enzymes that degrade SP are neutral endopeptidase (NEP) [ 24 ], SP degrading enzyme (SP-DE) [ 25 ] and angiotensin-converting enzyme (ACE) [ 26 ]; all of these enzymes cleave SP’s carboxyl-terminal active site and hence seriously compromise the bioavailability of SP.…”

Section: Introductionmentioning

confidence: 99%

A Chitosan—Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide

et al. 2017

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Currently, there is considerable interest in developing innovative biodegradable nanoformulations for controlled administration of therapeutic proteins and peptides. Substance P (SP) is a neuropeptide of 11 amino acids that belongs to the tachykinins family and it plays an important role in wound healing. However, SP is easily degradable in vivo and has a very short half-life, so the use of chitosan-based nanocarriers could enhance its pharmaceutical properties. In light of the above, the aim of this work was to produce and characterize chitosan-coated liposomes loaded with SP (SP-CH-LP) as novel biomaterials with potential application in mucosal wound healing. The loaded system’s biophysical properties were characterized by dynamic light scattering with non-invasive back scattering (DLS-NIBS), mixed mode measurements and phase analysis light scattering (M3-PALS) and high performance liquid chromatography with ultraviolet/visible light detection (HPLC-UV/VIS). Then, the efficacy of the obtained nanoformulations was examined via proof-of-principle experiments using in vitro cell assays. These assays showed an increment on cell motility and proliferation after treatment with free and encapsulated neuropeptides. Additionally, the effect of SP on wound healing was enhanced by the entrapment on CH-LP. Overall, the amenability of chitosan-based nanomaterials to encapsulate peptides and proteins constitutes a promising approach towards potential novel therapies to treat difficult wounds.

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Section: Introductionmentioning

confidence: 99%

A Chitosan—Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide

et al. 2017

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“…This is an important observation since it has already been suggested that the relative expression of tachykinin peptides and their C‐terminal fragments will influence pain transmission mechanisms, including pronoceptiveand antinociceptive actions. Furthermore, other C‐ and N‐terminal NPK or NKA fragments may have significant biological activity; however, this remains to be systematically investigated (Jonsson, ; Saidi et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the metabolic stability of NPK and NKA was assessed. The depletion profile was used to determine the metabolic stability of each peptide in rat spinal cord S9 fraction suspensions using a first-order kinetic model (Saidi, Kamali, & Beaudry, 2016).…”

Section: Metabolism Studymentioning

confidence: 99%

Characterization of neuropeptide K processing in rat spinal cord S9 fractions using high‐resolution quadrupole–Orbitrap mass spectrometry

Salem

Nkambeu

Beaudry

2018

Biomedical Chromatography

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Tachykinins are a family of pronociceptive neuropeptides with a specific role in pain and inflammation. Several mechanisms regulate endogenous tachykinins levels, including the differential expression of protachykinin mRNA and the controlled secretion of tachykinin peptides from neurons. We suspect that proteolysis regulates extracellular neuropeptide K (NPK) and neurokinin A (NKA) concentrations and NPK is a precursor of NKA. Here, we provide evidence that proteolysis controls NPK and NKA levels in the spinal cord, leading to the formation of active C-terminal peptide fragments. Using high-resolution mass spectrometry, specific tachykinin fragments were identified and characterized. The metabolic stability in rat spinal cord fractions of NPK and NKA was very short, resulting in half-lives of 1.9 and 2.2 min respectively. Following the degradation of NPK, several C-terminal fragments were identified, including NPK , NKA, NKA , NKA , NKA and NKA , which conserve affinity for the neurokinin 2 receptor but also for the neurokinin 1 receptor. Interestingly, the same fragments were identified following the degradation of NKA. A specific proprotein convertases inhibitor was used and showed a significant reduction in the rate of formation of NKA, providing strong evidence that proprotein convertase is involved in C-terminal processing of NPK in the spinal cord, leading to the formation of NKA.

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“…Additionally, due to oxidative reactions, which reduce the SP activity by up to 3-fold, Substance P is unstable during the production and storage [ 84 ]. The half-life time of SP is very short, from seconds to minutes [ 85 , 86 , 87 ]. Therefore, it is necessary to develop new SP formulations to improve its stability.…”

Section: Advanced Formulations Of Substance P For Topical and Systemic Deliverymentioning

confidence: 99%

The Regenerative Potential of Substance P

Redkiewicz

2022

IJMS

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Wound healing is a highly coordinated process which leads to the repair and regeneration of damaged tissue. Still, numerous diseases such as diabetes, venous insufficiencies or autoimmune diseases could disturb proper wound healing and lead to chronic and non-healing wounds, which are still a great challenge for medicine. For many years, research has been carried out on finding new therapeutics which improve the healing of chronic wounds. One of the most extensively studied active substances that has been widely tested in the treatment of different types of wounds was Substance P (SP). SP is one of the main neuropeptides released by nervous fibers in responses to injury. This review provides a thorough overview of the application of SP in different types of wound models and assesses its efficacy in wound healing.

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Characterization of Substance P processing in mouse spinal cord S9 fractions using high-resolution Quadrupole-Orbitrap mass spectrometry

Cited by 15 publications

References 37 publications

A Chitosan—Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide

A Chitosan—Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide

Characterization of neuropeptide K processing in rat spinal cord S9 fractions using high‐resolution quadrupole–Orbitrap mass spectrometry

The Regenerative Potential of Substance P

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