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Romanian Journal of Internal Medicine

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Caspases, Cell Death and Diabetic Nephropathy

Elena Bălăşescu
  • University of Medicine and Pharmacy, Department of Pathophysiology, Bucharest, Romania
/ Daniela Adriana Ion
  • University of Medicine and Pharmacy, Department of Pathophysiology, Bucharest, Romania
/ Mirela Cioplea
  • Corresponding author
  • “Carol Davila” University of Medicine and Pharmacy, Department of Pathology, Bucharest, Romania
  • Email:
/ Sabina Zurac
  • “Carol Davila” University of Medicine and Pharmacy, Department of Pathology, Bucharest, Romania
  • “Colentina” University Hospital, Department of Pathology
Published Online: 2015-12-10 | DOI: https://doi.org/10.1515/rjim-2015-0038

Abstract

Diabetic Nephropathy. In 2014 (according to data published by the World Health Organization) 9% of the global population was affected by Diabetes which was considered to be directly responsible for 1.5 million deaths just two years prior (in 2012). From the entire number of patients suffering from diabetes, approximately a quarter of them develop renal affection. Diabetic nephropathy has similar physiopathology mechanisms and ultrastructural changes in cell injury characteristics in both Type 1 and Type 2 diabetes.

Cell Death. Cell Death was less studied in the renal diabetic disease, although it could represent an important pathogenic mechanism in the appearance and progression of nephropathy. At renal level the cellular loss can be explained by several mechanisms; different stimuli with cellular lesion potential can trigger apoptosis signaling with appearance of regulatory proteins having a double role (they participate in the initiation of the apoptosis path and cell death or in the ending of this process). The types of Cell Death and their relative proportion between themselves in the renal tissue have not been completely elucidated.

Caspases. Discovered in the middle of the 1990’s, Caspases are a part of the cysteine proteases family and play a role in numerous aspects of physiology (having a role in development, aging and apoptosis), but also in aspects of physiopathology of several degenerative affections, autoimmune diseases, oncologic diseases – having an important part in apoptosis, necrosis and also inflammation.

Nefropatia diabetică. În anul 2014 (conform datelor publicate de Organizaţia Mondială a Sănătăţii), 9% din populaţia adultă a globului a fost afectată de diabet, care a fost considerat direct responsabil de 1,5 milioane de decese cu doar doi ani în urmă (în anul 2012). Din totalitatea pacienţilor cu diabet, aproximativ un sfert dezvoltă în timp afectare renală. Nefropatia diabetică are caracteristici similare din punct de vedere al mecanismelor fiziopatologice şi leziunilor ultrastructurale, atât în tipul 1 cât şi în tipul 2 de diabet zaharat. În cazurile de diabet tip 2 există însă posibilitatea ca rinichiul să fie afectat suplimentar de unii factori nocivi de tipul obezităţii, hipertensiunii arteriale, dislipidemiei şi bolii renale ischemice macrovasculare survenite independent de prezenţa diabetului.

Modificările morfologice specifice se regăsesc la nivelul tuturor structurilor renale (glomerulare, tubulare, vasculare, interstiţiale), determinând o constelaţie de aspecte imunohistochimice caracteristice diabetului, un eveniment cheie fiind reprezentat de depleţia celulară.

Moartea celulară. Moartea celulară a fost puţin studiată în boala renală diabetică, deşi ar putea reprezenta un mecanism patogenic important în apariţia şi progresia nefropatiei. La nivel renal pierderea celulară poate fi explicată prin mai multe mecanisme; diferiţi stimuli cu potenţial lezional celular pot declanşa semnalizarea apoptotică cu apariţia de proteine reglatoare cu dublu rol (participă la iniţierea căilor apoptozei şi la moartea celulară sau la oprirea acestui proces). Tipurile de moarte celulară precum şi proporţia relativă dintre acestea în ţesutul renal (apoptoză, necroză, autofagie, catastrofă mitotică), nu au fost pe deplin elucidate. Fenomenele care conduc la moartea celulară depind de tipul şi intensitatea semnalelor nocive, tipul de celulă afectată, dar şi de bagajul energetic al acesteia.

Caspazele. Descoperite la mijlocul anilor 1990, caspazele fac parte din familia cistein-proteazelor şi sunt implicate în numeroase aspecte ale fiziologiei (având rol în dezvoltare, îmbătrânire şi apoptoză), dar şi ale fiziopatologiei unor afecţiuni degenerative, boli autoimune, afecţiuni oncologice - având un rol esenţial atât în apoptoză şi necroză, cât şi în inflamaţie. Termenul de caspază provine de la C-simbol al cisteinei care este localizată în centrul activ al enzimei, ASP – acidul aspartic (substratul este clivat specific imediat după acidul aspartic), AZĂ – protează.

Keywords: diabetic nephropathy; cell death; caspases

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About the article

Received: 2015-04-28

Published Online: 2015-12-10

Published in Print: 2015-12-01



Citation Information: Romanian Journal Of Internal Medicine, ISSN (Online) 1220-4749, DOI: https://doi.org/10.1515/rjim-2015-0038. Export Citation

© 2015 Elena Bălăşescu et al., published by De Gruyter Open. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

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