scholarly journals Cathepsin D—Managing the Delicate Balance

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 837
Author(s):  
Olja Mijanovic ◽  
Anastasiia I. Petushkova ◽  
Ana Brankovic ◽  
Boris Turk ◽  
Anna B. Solovieva ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Neurodegenerative Disorders ◽  
Protein Turnover ◽  
Cathepsin D ◽  
Neuronal Ceroid Lipofuscinosis ◽  
The Other ◽  
Regulation Function ◽  
Lysosomal Proteases ◽  
Structure Regulation ◽  
Human Cathepsin

Lysosomal proteases play a crucial role in maintaining cell homeostasis. Human cathepsin D manages protein turnover degrading misfolded and aggregated proteins and favors apoptosis in the case of proteostasis disruption. However, when cathepsin D regulation is affected, it can contribute to numerous disorders. The down-regulation of human cathepsin D is associated with neurodegenerative disorders, such as neuronal ceroid lipofuscinosis. On the other hand, its excessive levels outside lysosomes and the cell membrane lead to tumor growth, migration, invasion and angiogenesis. Therefore, targeting cathepsin D could provide significant diagnostic benefits and new avenues of therapy. Herein, we provide a brief overview of cathepsin D structure, regulation, function, and its role in the progression of many diseases and the therapeutic potentialities of natural and synthetic inhibitors and activators of this protease.

The 52K cathepsin-D of breast cancer: structure, regulation, function and clinical value

1988 ◽  
pp. 207-221 ◽  
Author(s):  
Henri Rochefort ◽  
Patrick Augereau ◽  
Françoise Capony ◽  
Marcel Garcia ◽  
Vincent Cavailles ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cathepsin D ◽  
Clinical Value ◽  
Regulation Function ◽  
Structure Regulation

Processing of surfactant protein B proprotein by a cathepsin D-like protease

1992 ◽  
Vol 263 (1) ◽  
pp. L95-L103 ◽  
Author(s):  
T. E. Weaver ◽  
S. Lin ◽  
B. Bogucki ◽  
C. Dey
Keyword(s):  
Epithelial Cell ◽  
Cell Membrane ◽  
Cathepsin D ◽  
Surfactant Protein ◽  
Membrane Preparation ◽  
Aspartyl Protease ◽  
Type Ii ◽  
Surfactant Protein B ◽  
Type Ii Cell ◽  
Cell Membrane Preparation

Surfactant protein B (SP-B) is a hydrophobic peptide of relative molecular weight (M(r)) = 8,000 that is associated with pulmonary surfactant phospholipids. SP-B is synthesized by the alveolar type II epithelial cell as a proprotein of M(r) = 42,000 which requires at least two proteolytic cleavages to generate the 79 residue mature SP-B peptide. We have previously reported that cleavage of the NH2-terminal propeptide, to generate a processing intermediate of M(r) = 25,000, occurs in close temporal approximation to secretion. In the present study we demonstrate that SP-B proprotein, isolated from stably transfected Chinese hamster ovary cells, is processed to M(r) = 25,000 by a crude type II cell membrane fraction but not by intact type II cells or type II cell conditioned media. In vitro processing of the proprotein by the type II cell membrane preparation resulted in release of a single peptide of M(r) = 16,000–17,000, which was detected by antiserum directed against antigenic epitopes in propeptide of the precursor. SP-B processing activity was extracted by Na2CO3 lysis of the type II cell membrane preparation, had a pH optimum of 5.0–6.0, and was inhibited by 10(-7) M pepstatin A, suggesting that the NH2-terminal peptide of the precursor is cleaved by an aspartyl protease. Consistent with this hypothesis, processing of SP-B by a crude type II cell membrane preparation was blocked by antiserum directed against the aspartyl protease cathepsin D; further, purified cathepsin D efficiently processed the SP-B precursor to M(r) = 25,000. Collectively these results suggest that cleavage of the NH2-terminal propeptide of the SP-B precursor is mediated by cathepsin D or a cathepsin D-like protease localized within the secretory pathway of the type II epithelial cell.

scholarly journals The Relationships between Cholesterol and Suicide: An Update

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Domenico De Berardis ◽  
Stefano Marini ◽  
Monica Piersanti ◽  
Marilde Cavuto ◽  
Giampaolo Perna ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Membrane ◽  
The Other ◽  
Core Component ◽  
Cell Membrane Stability ◽  
Cholesterol Levels ◽  
The Central Nervous System ◽  
Larger Sample

Cholesterol is a core component of the central nervous system, essential for the cell membrane stability and the correct functioning of neurotransmission. It has been observed that cholesterol may be somewhat associated with suicidal behaviours. Therefore, the aim of this paper was to elucidate current facts and views about the role of cholesterol levels in mood disorders. The majority of the studies reviewed in the present paper suggest an interesting relationship between cholesterol (especially lower levels) and suicidality. On the other hand, particularly during the last years, relationships between serum cholesterol and suicidality were doubted on the basis of some recent studies that have not found any correlation. However, the debate on relationships between cholesterol and suicide is open and longitudinal studies on a larger sample of patients are needed to further clarify this important issue.

Design of sensitive fluorogenic substrates for human cathepsin D

FEBS Letters ◽  
1997 ◽  
Vol 413 (2) ◽  
pp. 379-384 ◽  
Author(s):  
Sergei V. Gulnik ◽  
Leonid I. Suvorov ◽  
Pavel Majer ◽  
Jack Collins ◽  
Bradley P. Kane ◽  
...  
Keyword(s):  
Cathepsin D ◽  
Fluorogenic Substrates ◽  
Human Cathepsin

New uses of Melatonin as a Drug, a Review

2022 ◽  
Vol 29 ◽  
Author(s):  
Miroslav Pohanka
Keyword(s):  
Cell Cycle ◽  
Circadian Rhythm ◽  
Sleep Disorder ◽  
Neurodegenerative Disorders ◽  
Melatonin Receptors ◽  
The Other ◽  
Basic Facts ◽  
Regulation Of Cell Cycle ◽  
Lifestyle Diseases

Abstract: Melatonin is a simple compound with a proper chemical name N-acetyl-5-methoxy tryptamine and known as a hormone controlling circadian rhythm. Humans produce melatonin at night which is the reason for sleeping in the night and awakening over the day. Melatonin interacts with melatonin receptors MT1 and MT2 but it was also revealed that melatonin is a strong antioxidant and it also has a role in regulation of cell cycle. Currently, melatonin is used as a drug for some types of sleep disorder but the recent research points to the fact that melatonin can also serve for the other purposes including prophylaxis or therapy of lifestyle diseases, cancer, neurodegenerative disorders and exposure to chemicals. This review summarizes basic facts and direction of the current research on melatonin. The actual literature was scrutinized for the purpose of this review.

Rotary movements and fluid membranes in termite flagellates

1976 ◽  
Vol 20 (3) ◽  
pp. 619-638
Author(s):  
S.L. Tamm ◽  
S. Tamm
Keyword(s):  
Plasma Membrane ◽  
Comparative Analysis ◽  
Cell Membrane ◽  
Shear Zone ◽  
Surrounding Medium ◽  
The Other ◽  
Visual Evidence ◽  
Fluid Membranes ◽  
Internal Motor ◽  
Rotary Motor

We previously described a remarkable type of cell motility that provided direct, visual evidence for the fluid nature of cell membranes. The movement involved continual, unidirectional rotation of one part of a protozoan, including the plasma membrane and cytoplasmic organelles, in relation to a neighbouring part. The cell membrane in the ‘shear zone’ appeared continuous with that of the rest of the cell. The rotary motor consisted, at least in part, of a non-contractile, microtubular axostyle which extended centrally through the cell. The protozoan was a devescovinid flagellate found in the hindgut of a Florida termite. In this paper, we have confirmed earlier reports of this type of motility in other kinds of devescovinids from Australian termites. By demonstrating continuity of the plasma membrane in the shear zone of the Australian devescovinids as well, we have obtained additional examples that provide direct, visual evidence for fluid membranes. A comparative analysis of rotational motility in various devescovinids revealed 2 different kinds of rotary mechanisms. Hyperdevescovina probably have an internal motor, in which one part of the cell exerts forces against another part, as in the Florida termite devescovinid. Devescovina species, on the other hand, have an external motor, in which flagellar and/or papillar movements exert forces against the surrounding medium. The structure of the axostyle in different devescovinids was compared, and its role in rotational motility discussed with respect to the behavioural data.

Ketoconazole - an antifungal drug for oral use

1981 ◽  
Vol 19 (23) ◽  
pp. 91-92
Keyword(s):  
Antifungal Activity ◽  
Cell Membrane ◽  
Oral Administration ◽  
Antifungal Agent ◽  
Systemic Effect ◽  
Antifungal Drug ◽  
The Other ◽  
Membrane Synthesis ◽  
Fungal Cell

Ketoconazole (Nizoral - Janssen) is a new antifungal agent. Like the other imidazoles with antifungal activity such as miconazole,1 clotrimazole2 and econazole,3 it acts by inhibiting fungal cell-membrane synthesis.4 It is well absorbed and exerts a systemic effect; it is thus suitable for oral administration.

scholarly journals A novel cathepsin D mutation in 2 siblings with late infantile neuronal ceroid lipofuscinosis

2019 ◽  
Vol 5 (3) ◽  
pp. e302 ◽  
Author(s):  
Jineesh Thottath ◽  
Shamsudheen Karuthedath Vellarikkal ◽  
Rijith Jayarajan ◽  
Ankit Verma ◽  
Manu Manamel ◽  
...  
Keyword(s):  
Cathepsin D ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Infantile Neuronal Ceroid Lipofuscinosis ◽  
Ceroid Lipofuscinosis

Steps in p-aminohippurate transport by kidney slices

1958 ◽  
Vol 196 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Ernest C. Foulkes ◽  
Benjamin F. Miller
Keyword(s):  
Cell Membrane ◽  
Transport System ◽  
Rate Constants ◽  
Extracellular Space ◽  
Concentration Ratio ◽  
Tissue Concentration ◽  
The Other ◽  
Facilitated Diffusion ◽  
Tubular Lumen ◽  
Cortical Slices

The existence of two intracellular fractions of PAH was demonstrated in renal cortical slices of the rabbit on incubation with C14-labeled PAH. One of these fractions is rapidly diffusible and rapidly equilibrates with extracellular PAH. The other fraction, in contrast, diffuses and equilibrates slowly; it is responsible for the high slice to medium concentration ratio of PAH. On the basis of these results a model of the PAH transport system in slices is proposed. This consists of step I, the diffusion of PAH from the medium into the extracellular space in the tissue; there follows step II, a facilitated diffusion step at the peritubular cell membrane; within the cell step III builds up a high tissue concentration of PAH; finally step IV transfers PAH across the luminal border of the cell into the tubular lumen from which it may diffuse back into the medium. Experiments were designed in which each of these steps could be measured individually and their rate constants determined. Alteration of the value of these rate constants by specific drugs localizes the action of such compounds at the peritubular cell membrane (Benemid, 9-alphafluorohydrocortisone) or at the level of both steps II and III in the case of DNP, octanoate and Diodrast. An explanation is also offered for the effect of cold on PAH influx and efflux. It can be calculated that the contribution of step IV to the turnover of PAH in slices is not quantitatively significant.

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