HlCPL-A, a cathepsin L-like cysteine protease from the ixodid tick Haemaphysalis longicornis, modulated midgut proteolytic enzymes and their inhibitors during blood meal digestion

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.

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A cathepsin L-like cysteine protease is conserved among Babesia equi isolates

Molecular and Biochemical Parasitology ◽

10.1016/s0166-6851(01)00423-6 ◽

2002 ◽

Vol 119 (2) ◽

pp. 295-300 ◽

Cited By ~ 7

Author(s):

Patricia J Holman ◽

Marlene M Hsieh ◽

Jessica L Nix ◽

Kylie G Bendele ◽

Gerald G Wagner ◽

...

Keyword(s):

Cysteine Protease ◽

Cathepsin L ◽

Babesia Equi

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Boophilus microplus cathepsin L-like (BmCL1) cysteine protease: Specificity study using a peptide phage display library

Veterinary Parasitology ◽

10.1016/j.vetpar.2011.04.003 ◽

2011 ◽

Vol 181 (2-4) ◽

pp. 291-300 ◽

Cited By ~ 17

Author(s):

Renan O. Clara ◽

Tatiane S. Soares ◽

Ricardo J.S. Torquato ◽

Cássia A. Lima ◽

Renata O.M. Watanabe ◽

...

Keyword(s):

Phage Display ◽

Cysteine Protease ◽

Cathepsin L ◽

Phage Display Library ◽

Boophilus Microplus ◽

Peptide Phage Display ◽

Specificity Study ◽

Protease Specificity

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Studies of Inhibitory Mechanisms of Propeptide-Like Cysteine Protease Inhibitors

Enzyme Research ◽

10.1155/2014/848937 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Bui T. T. Nga ◽

Yuki Takeshita ◽

Misa Yamamoto ◽

Yoshimi Yamamoto

Keyword(s):

Protease Inhibitors ◽

Cysteine Protease ◽

Cathepsin L ◽

Cysteine Residue ◽

Cysteine Protease Inhibitor ◽

Inhibition Mechanism ◽

Cysteine Protease Inhibitors ◽

Inhibitory Potency ◽

Inhibitory Mechanisms

Mouse cytotoxic T-lymphocyte antigen-2α (CTLA-2α), Drosophila CTLA-2-like protein (crammer), and Bombyx cysteine protease inhibitor (BCPI) belong to a novel family of cysteine protease inhibitors (I29). Their inhibitory mechanisms were studied comparatively. CTLA-2α contains a cysteine residue (C75), which is essential for its inhibitory potency. The CTLA-2α monomer was converted to a disulfide-bonded dimer in vitro and in vivo. The dimer was fully inhibitory, but the monomer, which possessed a free thiol residue, was not. A disulfide-bonded CTLA-2α/cathepsin L complex was isolated, and a cathepsin L subunit with a molecular weight of 24,000 was identified as the interactive enzyme protein. Crammer also contains a cysteine residue (C72). Both dimeric and monomeric forms of crammer were inhibitory. A crammer mutant with Cys72 to alanine (C72A) was fully inhibitory, while the replacement of Gly73 with alanine (G73A) caused a significant loss in inhibitory potency, which suggests a different inhibition mechanism from CTLA-2α. BCPI does not contain cysteine residue. C-terminal region (L77-R80) of BCPI was essential for its inhibitory potency. CTLA-2α was inhibitory in the acidic pH condition but stabilized cathepsin L under neutral pH conditions. The different inhibition mechanisms and functional considerations of these inhibitors are discussed.

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Serine hydroxymethyltransferase controls blood-meal digestion in the midgut of Aedes aegypti mosquitoes

Parasites & Vectors ◽

10.1186/s13071-019-3714-2 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Xuemei Li ◽

Jinyu Yang ◽

Qian Pu ◽

Xinyue Peng ◽

Lili Xu ◽

...

Keyword(s):

Aedes Aegypti ◽

Blood Meal ◽

Digestive Enzymes ◽

Egg Production ◽

Sequence Similarity ◽

Mrna Level ◽

Serine Hydroxymethyltransferase ◽

Blood Protein ◽

Transcriptional Expression ◽

Blood Meal Digestion

Abstract Background Female Aedes aegypti mosquitoes are vectors of arboviruses that cause diverse diseases of public health significance. Blood protein digestion by midgut proteases provides anautogenous mosquitoes with the nutrients essential for oocyte maturation and egg production. Midgut-specific miR-1174 affects the functions of the midgut through its target gene serine hydroxymethyltransferase (SHMT). However, less is known about SHMT-regulated processes in blood digestion by mosquitoes. Methods RNAi of SHMT was realized by injection of the double-stranded RNA at 16 h post-eclosion. The expression of SHMT at mRNA level and protein level was assayed by real-time PCR and Western blotting, respectively. Statistical analyses were performed with GraphPad7 using Student’s t-test. Results Here, we confirmed that digestion of blood was inhibited in SHMT RNAi-silenced female A. aegypti mosquitoes. Evidence is also presented that all SHMT-depleted female mosquitoes lost their flight ability and died within 48 h of a blood meal. Furthermore, most examined digestive enzymes responded differently in their transcriptional expression to RNAi depletion of SHMT, with some downregulated, some upregulated and some remaining stable. Phylogenetic analysis showed that transcriptional expression responses to SHMT silence were largely unrelated to the sequence similarity between these enzymes. Conclusions Overall, this research shows that SHMT was expressed at a low level in the midgut of Aedes aegypti mosquitoes, but blood-meal digestion was inhibited when SHMT was silenced. Transcriptional expressions of different digestive enzymes were affected in response to SHMT depletion, suggesting that SHMT is required for the blood-meal digestion in the midgut and targeting SHMT could provide an effective strategy for vector mosquito population control.

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Identification and characteristics of a cathepsin L-like cysteine protease from Clonorchis sinensis

Parasitology Research ◽

10.1007/s00436-019-06223-y ◽

2019 ◽

Vol 118 (3) ◽

pp. 829-835 ◽

Cited By ~ 2

Author(s):

Changling Ma ◽

Kai Liang ◽

Lili Tang ◽

Shanshan He ◽

Xiaoquan Liu ◽

...

Keyword(s):

Cysteine Protease ◽

Cathepsin L ◽

Clonorchis Sinensis

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Cathepsin L—a novel cysteine protease from Haemaphysalis flava Neumann, 1897

Parasitology Research ◽

10.1007/s00436-019-06271-4 ◽

2019 ◽

Vol 118 (5) ◽

pp. 1581-1592 ◽

Cited By ~ 2

Author(s):

Yali Sun ◽

Lan He ◽

Long Yu ◽

Jiaying Guo ◽

Zheng Nie ◽

...

Keyword(s):

Cysteine Protease ◽

Cathepsin L ◽

Haemaphysalis Flava

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Presence of Anti-cystatin C–positive Dendritic Cells or Macrophages and Localization of Cysteine Proteases in the Apical Bud of the Enamel Organ in the Rat Incisor

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.4a6533.2005 ◽

2005 ◽

Vol 53 (5) ◽

pp. 643-651 ◽

Cited By ~ 1

Author(s):

Sumio Nishikawa

Keyword(s):

Dendritic Cells ◽

Cystatin C ◽

Cysteine Protease ◽

Cathepsin L ◽

Cysteine Proteases ◽

Cysteine Protease Inhibitor ◽

Enamel Organ ◽

Apical Bud ◽

Apical Buds ◽

Proliferation And Differentiation

Cystatin C, a cysteine protease inhibitor, was examined in the apical buds of rat incisors by immunohistochemistry, because in transition and maturation zones most of the dendritic cells in the papillary layer are anti-cystatin C–positive. Anti-cystatin C–labeled cells were sparse and localized to the proliferation and differentiation zones, constituting the apical bud of 5-week-old rat incisors. These cells were considered macrophages or dendritic cells, based on their reactivity with OX6 and ED1, as well as their ultrastructure. Basement membrane at the periphery of apical bud was also labeled by anti-cystatin C antibody. The apical buds included a few apoptotic fragments and weak reactivity with antibody to cathepsin L, a cysteine protease. Reactivity to anti-cystatin C and anti-cathepsin ∗∗∗L antibodies was also detected in the apical bud of newborn rat incisors. These results suggest that the cystatin C–positive macrophages or dendritic cells are involved in normal incisor formation. They may be related to the clearance of apoptotic cells or protection from putative cysteine protease activity.

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