The Noncollagenous Proteins of the Intervertebral Disc *
Peter Ghosh in The Biology of the Intervertebral Disc, 2019
Work on disc proteinases, prior to 1975, was concerned mainly with the autolytic changes which occurred most readily at an acid pH.184,360,361 Dziewiatowski et al.362 reported significant degradation of denatured hemoglobin at pH 3.6 by extracts of disc autopsy specimens. Since hemoglobin was the most sensitive protein substrate known for cathepsin D (which has a pH optimum between 2.8 and 5), it seems likely that this was the proteinase responsible.363 Using prolapsed disc material obtained at the time of surgery, Nay lor et al.184 also demonstrated that autolysis of disc tissues could occur at an acid pH. The enzymes responsible were not studied in detail, but these authors did confirm the presence of cathepsin D in these preparations by using specific antibodies. Additional studies by this group showed that enzyme activity at pH 4 to 5 was enhanced by EDTA and DTT. Under these conditions, degradation of PG and the synthetic substrates, benzoyl arginine nitroanilide and naphthylamide, readily occurred. As this latter substrate was particularly sensitive for cathepsin B,364 it suggested the presence of thiol proteinases with cathepsin B-like specificity within disc tissues.
2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Environmental Antiestrogens:Characterization and Mechanism of Action
Rajesh K. Naz in Endocrine Disruptors, 2004
At least two function iDREs have been identified within the −200 to −100 region of the cathepsin D gene promoter; and iDRE1 has been extensively characterized using the wild-type Sp1(N)23ERE(2) oligonucleotide in gel mobility shift and transient transfection assays (see Figure 8.5B). Interaction of the liganded AhR complex with iDRE1 results in disruption of the ER/Sp1-DNA complex and loss of transac-tivation in transient transfection assays. Moreover, using a bromodeoxyuridine-substituted Sp1(N)23ERE(2) oligonucleotide, the AhR complex could be crosslinked to the DNA sequence.133 In contrast, an Sp1(N)23ERE(2) oligonucleotide containing a mutant iDRE motif bound nuclear extracts to form an ER/Sp1-DNA complex and was E2-responsive in transient transfection assays; however, the inhibitory effects of the AhR complex were not observed in these studies. A comparable approach has also been utilized for characterizing other functional iDREs in the pS2, Hsp 27, and c-fos gene promoters. Current research is focused on identifying functional iDREs in other genes and investigating alternative mechanisms associated with AhR-mediated antiestrogenic activity.
The Melanotropic Peptides: Structure and Chemistry
Mac E. Hadley in The Melanotropic Peptides, 1988
Mammalian β-MSHs consist of 18 amino acid residues, except for the human hormone. Human β-MSH has an additional tetrapeptide, Ala-Glu-Lys-Lys, attached at the N-terminus of monkey β-MSH. However, the adult human pituitary gland is unusual in not having an intermediate lobe and is believed to lack β-MSH. Therefore, recovery of human β-MSH from adult pituitary extracts is thought to be an artifact of the isolation procedure. Indeed, Barat et al.32 showed that highly purified calf brain cathepsin D selectively splits Ala36-Ala37 and Leu77-Phe,78 and suggested that the formation of human β-MSH from β-LPH is due to the action of the enzyme during isolation procedure.
Cardio-protective effects of terminalia catappa leaves and terminalia chebula fruit extract in doxorubicin-induced cardiomyopathy in rats
Published in Biomarkers, 2022
Ramasamy Manikandan, Balamuralikrishnan Balasubramanian, Panneerselvam Punniyakotti, Arumugam Vijaya Anand, Arun Meyyazhagan, Shanmugam Velayuthaprabhu, Rengasamy Lakshminarayanan Rengarajan, Utthapon Issara, Wen-Chao Liu
In the present study, the Tct.LE and Tce.FE, propranolol enhances the activities of TCA cycle enzymes, these may improve the mitochondrial antioxidant defence system and overcome the complications with the decreased TCA cycle function. The treatment with Tct.LE and Tce.FE, propranolol may reduce the oxidative damage in the mitochondria and enhances the antioxidant status. The decrease in mitochondrial antioxidants could be due to the feedback inhibition or oxidative inactivation of enzyme protein caused by the excess ROS generation (Al-Assaf 2014). Cathepsin D is a lysosomal enzyme, which is present in all animal cells (Sudharsan 2006). It is mainly involved in the autophagic digestion of discrete parts of the cytoplasm and the proteins present in the myofibrillary and mitochondria. This type of lysosomal enzymes stimulates the oxygen radical; it disturbs the cardiac tissues. These are in agreement with Suchalatha and Devi (2005), who reported that the levels of β-D-glucuronidase and β-N-acetyl glucosaminidase levels are reduced in the T. chebula treats in the isoproterenol-induced cardiac damage in rats.
Circulating cathepsin B and D in pregnancy
Published in Journal of Obstetrics and Gynaecology, 2019
As no studies to-date has examined the plasma concentrations of cathepsins in the first and third trimesters in pregnancy, we reviewed MMPs and the associations with cathepsins in pregnancy. The function of cathepsin D is related to MMPs because this protease can activate MMPs either directly or indirectly (Hu et al. 2008). Cathepsin D also activates the precursor forms of other proteolytic enzymes, including MMPs. Cathepsin D is known to enhance proteolysis by degrading the proteolytic enzyme tissue inhibitors (Lenarcic et al. 1991; Pimenta et al. 2000). In an acute myocardial infarction, the plasma MMP-9 concentration is strongly positively correlated with the cathepsin levels (Shalia et al. 2012). One study found that the circulating level of MMP is dramatically increased during pregnancy (Tu et al. 1998). Specifically, the plasma concentration of MMP-9 increased 19-fold compared to the non-pregnant subjects, but remained unchanged throughout pregnancy because of the ongoing reorganisation of extracellular matrix in the uterus and placenta. Our finding that the plasma cathepsin D concentration is significantly increased in the third trimester might be related to the similar physiological increase in MMPs in pregnancy.
Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration
Published in Organogenesis, 2019
Yoshihiro Matsumoto, Tomoharu Yoshizumi, Takeo Toshima, Kazuki Takeishi, Takasuke Fukuhara, Shinji Itoh, Toru Ikegami, Yuji Soejima, Masaki Mori
Next, we examined the involvement of pathways in steatotic liver regeneration. In m+/m+ mice, the peak LC3-II level was observed at 12 h after 70% PH, while the p62 protein, which regulates ubiquitinated protein, was increased gradually at least 48 h. However, in db/db mice, the LC3-II level was higher and p62 expression was notably increased in db/db mice compared with m+/m+ mice (Fig. 3), while Atg5-12 expression levels were nearly equal in both groups. These results suggest that autophagosome formation is not suppressed, but autophagic proteolysis is inhibited in db/db mice compared with controls. Thus, the cathepsin D protein level, a proteinase of lysosomes, was evaluated. As expected, cathepsin D expression was suppressed in db/db mice compared with controls (Fig. 3).