Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3

Tian, Xin; Shi, Yongfeng; Liu, Ning; Yan, Youyou; Li, Tianyi; Hua, Peiyan; Liu, Bin

doi:10.3892/mmr.2016.5733

Cited by 30 publications

(16 citation statements)

References 35 publications

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“…Moderate hyperhomocysteinemia was revealed in patients with progressive clinical course of ASO. It is in accordance with the literature that endothelial dysfunction may lead to pro-atherogenic effects associated with hyperhomocysteinemia [21][22][23].…”

Section: Discussionsupporting

confidence: 92%

The condition of lipid metabolism, hemostasis and general homocysteine level as a manifestation of endothelial dysfunction at progressing course of atherosclerosis obliterans of the lower extremities

Дунаевская¹,

Antufrieva²

2017

Russ. Open Med. J.

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Abstract:The problems related to studying predictors of atherosclerosis obliterans (ASO) of the lower extremities are quite relevant due to high disability and lethality rate of patients belonging to this group. This study aimed to evaluate the values of lipid profile, general homocysteine and hemostasis in relation to the clinical course of ASO. Material and Methods -55 patients with ASO of the lower extremities were divided into two groups: 30 patients with no progressive clinical course, 25 patients with progressive clinical course. The group division was based on the anamnesis (duration of the disease, decrease of painless walking distance during the year, the length of effect lasting from conservative treatment). Data presented as median with lower and upper quartiles -Me (LQ, UQ). Results -As a result of research, there was a registration of moderate hyperhomocysteinemia -23.6 (20.1, 26.4) mkmol/l, as well as high values of triglycerides -2.10 (1.72, 2.51) mmol/l and low-density lipoproteins -4.48 (3.95, 6.44) mmol/l, against low values of high-density lipoproteins -1.14 (0.72, 1.40) mmol/l in lipid profile. Development of hypercoagulability and susceptibility to thrombosis in patients is manifestation of endothelial dysfunction, which plays a key role in progression of ASO of the lower extremities. Keywords: atherosclerosis obliterans, progressive course, hemostasis, lipid profile, homocysteineCite as Dunaevskaya SS, Antufrieva DA. The condition of lipid metabolism, hemostasis and general homocysteine level as a manifestation of endothelial dysfunction at progressing course of atherosclerosis obliterans of the lower extremities.

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Section: Discussionsupporting

confidence: 92%

The condition of lipid metabolism, hemostasis and general homocysteine level as a manifestation of endothelial dysfunction at progressing course of atherosclerosis obliterans of the lower extremities

Дунаевская¹,

Antufrieva²

2017

Russ. Open Med. J.

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“…Moreover, DAPK1 binds the full‐length microtubule‐associated protein 1B (MAP1B) by its kinase domain forming a stable immune complex under amino acid starvation conditions provoking membrane blebbing. MAP1B knockout using small interfering RNA (siRNA) attenuated DAPK1‐stimulated autophagy and membrane blebbing …”

Section: Dapks Cellular Functionsmentioning

confidence: 99%

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Farag

Roh

2018

Medicinal Research Reviews

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Serine/threonine kinases (STKs) represent the majority of discovered kinases to date even though a few Food and Drug Administration approved STKs inhibitors are reported. The third millennium came with the discovery of an important group of STKs that reshaped our understanding of several biological signaling pathways. This family was named death-associated protein kinase family (DAPK family). DAPKs comprise five members (DAPK1, DAPK2, DAPK3, DRAK1, and DRAK2) and belong to the calcium/calmodulin-dependent kinases domain. As time goes on, the list of biological functions of this family is constantly updated. The most extensively studied member is DAPK1 (based on the publications number and Protein Data Bank reported crystal structures) that plays fundamental biological roles depending on the cellular context. DAPK1 regulates apoptosis, autophagy, contributes to the pathogenesis of Alzheimer's disease, acts as a tumor suppressor, inhibits metastasis, mediates the body responses to viral infections, and regulates the synaptic plasticity and depression. For their biological roles, several DAPKs' modulators have been reported for treatment of many diseases as well as acting as probe compounds to facilitate the understanding of the biological functions elicited by this family. Despite that, the number of reported modulators is still limited and more research needs to be conducted on the discovery of novel strategies to activate or inhibit this family. In this report, we aim at drawing more attention to this family by reviewing the recent updates regarding the structure, biological roles, and regulation of this family. In addition, the small-molecule modulators of this family are reviewed in details with their potential therapeutic outcomes evaluated to help medicinal chemists develop more potent and selective possible drug candidates.

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“…Hcy-induced cell apoptosis has been studied in various cell types including neuronal [17], promyeloid [18], endothelial [19,20], and mesangial cells [21]. The study in mesangial cells showed that Hcy induces apoptosis by activating p38-mitogen-activeated protein kinase [21].…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulphide mitigates homocysteine-induced apoptosis and matrix remodelling in mesangial cells through Akt/FOXO1 signalling cascade

Majumder

Ren

Pushpakumar

et al. 2019

Cellular Signalling

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Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3

Cited by 30 publications

References 35 publications

The condition of lipid metabolism, hemostasis and general homocysteine level as a manifestation of endothelial dysfunction at progressing course of atherosclerosis obliterans of the lower extremities

The condition of lipid metabolism, hemostasis and general homocysteine level as a manifestation of endothelial dysfunction at progressing course of atherosclerosis obliterans of the lower extremities

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Hydrogen sulphide mitigates homocysteine-induced apoptosis and matrix remodelling in mesangial cells through Akt/FOXO1 signalling cascade

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