On the degradation of intracellular RNA by ribonucleases

García‐Segura, Juan M.; Jesus, Margarita C. De; Fominaya,; Orozco, Modesto; Gavilanes, José G.

doi:10.1016/0020-711x(86)90110-2

Cited by 7 publications

(5 citation statements)

References 12 publications

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“…It can be argued that this optimum pH may be different from the intracellular one. Nevertheless, it has been demonstrated that the possibility of local pH variations related to ribonucleolytic activity of enzymes could result in an optimum pH lower that the physiological pH (63). Thus, the presence of different electronic environments in the proximity of the rRNA scissile bond should be taken into account and merits further investigations so the in vivo R-sarcin activity can be better understood.…”

Section: Discussionmentioning

confidence: 99%

Characterization of pK_a Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

et al. 1998

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The electrostatic behavior of titrating groups in alpha-sarcin was investigated using 1H NMR spectroscopy. A total of 209 chemical shift titration curves corresponding to different protons in the molecule were determined over the pH range of 3.0-8.5. Nonlinear least-squares fits of the data to simple relationships derived from the Henderson-Hasselbalch equation led to the unambiguous determination of pKa values for all glutamic acid and histidine residues, as well as for the C-terminal carboxylate and most of the aspartic acids in the free enzyme. The ionization constants of catalytically relevant histidines, His50 and His137, and glutamic acid, Glu96, in the alpha-sarcin-2'-GMP complex were also determined. The pKa values of 15 ionizable groups (C-carboxylate, six aspartic acids, four glutamic acids, and four histidines) were found to be close to their normal values. On the other hand, a number of side chain groups, including those in the active center, showed pKa values far from their intrinsic values. Thus, the pKa values for active site residues His50, Glu96, and His137 were 7.7, 5.2, and 5.8 in the free enzyme and 7.6, approximately 4.8, and 6.8 in the alpha-sarcin-2'-GMP complex, respectively. The pKa values and the activity profile against ApA, as a function of pH, are in agreement with the proposed enzymatic mechanism (in common with RNase T1 and the family of the microbial ribonucleases), in which Glu96 and His137 act as a general base and general acid, respectively. In almost all microbial ribonucleases, a Phe-His interaction is present, which affects the pKa of one of the His residues at the active site (His137). The absence of this interaction in alpha-sarcin would explain the lower pKa value of this His residue, and provides an explanation for the decreased RNase activity of this protein as compared to those of other microbial ribonucleases.

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Section: Discussionmentioning

confidence: 99%

Characterization of pK_a Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

et al. 1998

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“…The decrease in acid RNase activity in the muscle of 20GH mice suggests an inverse relation between high rates of protein synthesis and acid RNase activity, perhaps leading to spare muscle RNA for protein synthesis during catch-up growth. Since it has been suggested that RNase activity in animal cells may act indirectly to regulate protein synthesis by controlling RNA degradation [33], decreases in acid RNase activity in 20GH mice could be related to the maintenance or expansion of the RNA pool and indirectly contribute to increasing protein synthesis via mRNA maintenance in the cells [60]. GH could act through inhibitors synthesised de novo, as occurs in response to surgical trauma [61].…”

Section: Discussionmentioning

confidence: 98%

“…3.1.27.5.) activity was assayed according to the García-Segura et al [33] method. 0.1 mL of each supernatant obtained previously was mixed with 0.4 mL of 0.25 M Tris-acetate buffer, 0.2% BSA, pH 5.5.…”

Section: Enzyme and Protein Assaymentioning

confidence: 99%

The modulator effect of GH on skeletal muscle lysosomal enzymes is dietary protein dependent

López-Oliva

Agis-Torres

Muñoz-Martínez

2007

Growth Hormone & IGF Research

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“…(ii) The released RNase A will induce cytotoxicity by lysing intracellular RNA and then activating protein therapy. More importantly, the oxidation environment caused by CDT can in turn inhibit the activity of ribonuclease inhibitor (RI) 36,37 and reduce its inhibition to RNase A, finally realizing the synergistic enhancement effect of Scheme 1. Synthesis (A) and Schematic Illustration (B) of the Tannic Acid-Assisted Biomineralization RNase A/GOD@TA-Mn 2+ @CaCO 3 (RG@MT@C) for Encapsulation and Intracellular Delivery of Protein Enzymes and High Performance of Cancer Therapy protein therapy and CDT.…”

Section: ■ Introductionmentioning

confidence: 99%

“…(ii) The released RNase A will induce cytotoxicity by lysing intracellular RNA and then activating protein therapy. More importantly, the oxidation environment caused by CDT can in turn inhibit the activity of ribonuclease inhibitor (RI) , and reduce its inhibition to RNase A, finally realizing the synergistic enhancement effect of protein therapy and CDT. (iii) The released GOD will consume Glu to trigger starvation treatment, while the generated H 2 O 2 can further promote Mn 2+ -Fenton catalytic reaction to produce a large amount of highly toxic • OH.…”

Section: Introductionmentioning

confidence: 99%

Tannic Acid-Assisted Biomineralization Strategy for Encapsulation and Intracellular Delivery of Protein Drugs

Yin

Jing

et al. 2022

ACS Appl. Mater. Interfaces

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Protein therapy has been considered to be one of the most direct and safe ways to regulate cell function and treat tumors. However, safe and effective intracellular delivery of protein drugs is still a key challenge. Herein, we developed a tannic acid-assisted biomineralization strategy for the encapsulation and intracellular delivery of protein drugs. RNase A and glucose oxidase (GOD) were choose as the protein drug model. RNase A, GOD, TA, and Mn2+ are mixed in one pot to attain RG@MT, and CaCO3 coating is subsequently carried out to construct RG@MT@C through biomineralization. Once RG@MT@C is endocytosed, the acidic environment of the lysosome will dissolve the protective layer of CaCO3 and produce plenty of CO2 to cause lysosome bursting, ensuring the lysosome escape of the RG@MT@C and thus releasing the generated TA-Mn2+, RNase A, and GOD into the cytoplasm. The released substances would activate starvation therapy, chemodynamic therapy, and protein therapy pathways to ensure a high performance of cancer therapy. Due to simple preparation, low toxicity, and controlled release in the tumor microenvironment, we expect it can realize efficient and nondestructive delivery of protein drugs and meet the needs for precise, high performance of synergistically antitumor therapy in biomedical applications.

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On the degradation of intracellular RNA by ribonucleases

Cited by 7 publications

References 12 publications

Characterization of pK_a Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

Characterization of pK_a Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

The modulator effect of GH on skeletal muscle lysosomal enzymes is dietary protein dependent

Tannic Acid-Assisted Biomineralization Strategy for Encapsulation and Intracellular Delivery of Protein Drugs

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On the degradation of intracellular RNA by ribonucleases

Cited by 7 publications

References 12 publications

Characterization of pKa Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

Characterization of pKa Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

The modulator effect of GH on skeletal muscle lysosomal enzymes is dietary protein dependent

Tannic Acid-Assisted Biomineralization Strategy for Encapsulation and Intracellular Delivery of Protein Drugs

Contact Info

Product

Resources

About

Characterization of pK_a Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function

Characterization of pK_a Values and Titration Shifts in the Cytotoxic Ribonuclease α-Sarcin by NMR. Relationship between Electrostatic Interactions, Structure, and Catalytic Function