AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia

Sm, Yang; Zhao, Xinmei; Xu, Hui; Chen, Fan; Xu, Yitao; Li, Zhe; Sanchı́s, Daniel; Jin, Liang; Zhang, Yubin; Ye, Junmei

doi:10.3390/ijms18030565

Cited by 26 publications

(16 citation statements)

References 40 publications

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“…[ 64 ] Instead, AIF can migrate into the nucleus where induces caspase-independent chromatin condensation and large-scale DNA fragmentation following ischemia. [ 65 66 ] In addition, the association of cytochrome c with APAF-1 creates the apoptosome that recruits and active the procaspase-9 in caspase-9. Once activated, caspase-9 can activate effector caspase-3.…”

Section: Mitochondria Dysfunction Inducer Of Stress Disease and Deamentioning

confidence: 99%

Mitochondrial targeting as a novel therapy for stroke

et al. 2018

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Stroke is a main cause of mortality and morbidity worldwide. Despite the increasing development of innovative treatments for stroke, most are unsuccessful in clinical trials. In recent years, an encouraging strategy for stroke therapy has been identified in stem cells transplantation. In particular, grafting cells and their secretion products are leading with functional recovery in stroke patients by promoting the growth and function of the neurovascular unit – a communication framework between neurons, their supply microvessels along with glial cells – underlying stroke pathology and recovery. Mitochondrial dysfunction has been recently recognized as a hallmark in ischemia/reperfusion neural damage. Emerging evidence of mitochondria transfer from stem cells to ischemic-injured cells points to transfer of healthy mitochondria as a viable novel therapeutic strategy for ischemic diseases. Hence, a more in-depth understanding of the cellular and molecular mechanisms involved in mitochondrial impairment may lead to new tools for stroke treatment. In this review, we focus on the current evidence of mitochondrial dysfunction in stroke, investigating favorable approaches of healthy mitochondria transfer in ischemic neurons, and exploring the potential of mitochondria-based cellular therapy for clinical applications. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed.

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Section: Mitochondria Dysfunction Inducer Of Stress Disease and Deamentioning

confidence: 99%

Mitochondrial targeting as a novel therapy for stroke

et al. 2018

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“…In this regard, upon migration to the cytosol, Smac binds to and inhibits the inhibitor-of-apoptosis proteins (IAPs), which normally inhibit pro-caspase activation and caspases activity [54]. Conversely, AIF is characterized by the unique capacity to induce caspase-independent chromatin condensation and large-scale DNA fragmentation upon migration to the nucleus, in response to ischemia [55,56]. The formation of an apoptosome, which converts procaspase-9 to caspase-9, is catalyzed by the association of cytochrome c with APAF-1, and the subsequent activation of caspase 3.…”

Section: Mitochondria Etc and Oxphosmentioning

confidence: 99%

Understanding the Role of Dysfunctional and Healthy Mitochondria in Stroke Pathology and Its Treatment

Nguyen

Zarriello

Rajani

et al. 2018

Preprint

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Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

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“…Апоптоз является общебиологическим механизмом, ответственным за поддержание постоянства численности клеточных популяций, а также формообразование и выбраковку дефектных клеток. Нарушение регуляции апоптоза приводит к развитию заболеваний, связанных с усилением или, наоборот, ингибированием апоптоза [7][8][9][10].…”

Section: Introductionunclassified

“…Стадия реализации программы апоптоза (эффекторная) состоит в собственно гибели клетки, которая наступает вследствие активации протеолитического и нуклеолитического каскадов. Непосредственными исполнителями процесса «умерщвления» клетки являются Ca 2+ /Mg 2+ -зависимые эндонуклеазы (катализируют распад нуклеиновых кислот) и эффекторные каспазы (подвергают протеолитическому расщеплению различные белки, в том числе белки цитоскелета ядра, регуляторные белки и ферменты) [10,12]. Фермент эндонуклеаза, фрагментирующий ДНК, активируется при значительном повышении уровня зольного кальция в клетке.…”

Section: Introductionunclassified

“…Фермент эндонуклеаза, фрагментирующий ДНК, активируется при значительном повышении уровня зольного кальция в клетке. Увеличение содержания эндонуклеазы является обязательным маркером апоптоза, в начале которого отмечено увеличение цитоплазматического зольного кальция и изменение рН цитоплазмы, что запускает синтез АТФ -начало фрагментации ДНК [10,13,14].…”

Section: Introductionunclassified

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Pancreas Proapoptotic Proteases in Patients with Chronic Pancreatitis

Губергриц

Крылова²,

Gaĭdar

2019

Rossijskij žurnal gastroènterologii, gepatologii, koloproktolog

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Aim. To study features of localization of the DNA-ase I and endonuclease-G proapoptotic proteases in the pancreas in chronic pancreatitis (CP). Materials and methods. Histological pancreas preparations from 60 patients with various CP forms were studied: group I — 10 patients with obstructive CP; group II — 21 patients with calcific CP; group III — 13 patients with fibroparenchymal CP; group IV — 16 patients with CP complicated by pseudocyst. Pancreas biopsies were obtained during planned organ operations, as well as using a fine-needle biopsy under ultrasound control. Tissue material was fixed in Bowen medium. Microscopic tissue sections were prepared and subsequently stained with hematoxylin-eosin and by Mallory-Slinchenko. Immunohistochemical typing of proapoptotic proteases was performed according to the indirect avidin-streptavidin-peroxidase reaction (“Elite”, USA) using rabbit antibodies to DNA-I and endonuclease-G (“Chemicon”, USA, 1: 500 dilution — 1: 2000, incubation 12:00, + 4 °С).Results. Patients in all the groups demonstrated signs of chronic inflammation, with 31.7 % of cases showing signs of its exacerbation. Atrophic changes were found in most patients (96.7 %). No significant differences were observed with regard to the severity and frequency of fibrosis of various degrees in the groups: mild, moderate, severe and full fibrosis was detected in 6.7 %, 20.0 %, 16.7 % and 56.6 %, respectively. The study of the localization of proapoptotic nucleases in the structures of the pancreas showed proapoptotic nucleases of DNA-ase I to be exclusively located in the cytoplasm of pancreatic acinar cells. At all stages of CP fibrosis, single acinar cells with translocation of the nuclease from the cytoplasm into the cell nucleus were found in the lobes of the pancreas. Endonuclease-G was found in large numbers in the cytoplasm of pancreatic islets, with it lower number being detected in the cytoplasm of the epithelial cells of the ducts. Conclusions. In CP, proapoptotic proteases of DNase I and endonuclease G are expressed in the cytoplasm of cells located in different pancreas zones. Thus, DNase I is expressed in the cytoplasm of acinar cells, while endonuclease G is most typical for insular cells and those in the epithelium of the ducts. This proves the existence of various apoptosis mechanisms in the exo- and endocrine portions of the pancreas.

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AKT2 Blocks Nucleus Translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) While Promoting Caspase Activation during Cardiac Ischemia

Cited by 26 publications

References 40 publications

Mitochondrial targeting as a novel therapy for stroke

Mitochondrial targeting as a novel therapy for stroke

Understanding the Role of Dysfunctional and Healthy Mitochondria in Stroke Pathology and Its Treatment

Pancreas Proapoptotic Proteases in Patients with Chronic Pancreatitis

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