IQGAP1-dysfunction leads to induction of senescence in human vascular smooth muscle cells
| Autor: | Agata Klejman, Anna Bielak-Zmijewska, Krzysztof Skowronek, Natalia Achtabowska, Wioleta Grabowska, Malgorzata Calka |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Senescence Aging Chemokine Vascular smooth muscle Cell Myocytes Smooth Muscle CDC42 Cell Communication Biology Muscle Smooth Vascular 03 medical and health sciences 0302 clinical medicine IQGAP1 medicine Humans cdc42 GTP-Binding Protein Actin Cells Cultured Cellular Senescence Cell Proliferation beta-Galactosidase Phenotype Actins Cell biology 030104 developmental biology medicine.anatomical_structure ras GTPase-Activating Proteins biology.protein 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Mechanisms of ageing and development. 190 |
| ISSN: | 1872-6216 |
| Popis: | Cell senescence - an irreversible proliferation arrest - is one of the possible cellular responses to stress. There is a vast variety of stimuli, extrinsic and intrinsic, known to induce senescence, and several molecular pathways involved in the process; yet much still remains to be explained. Senescent cells can communicate with neighboring cells through secreted factors such as cytokines and chemokines. Several years ago it was shown that cells can also communicate in a more direct manner by an exchange of proteins via cellular bridges (CBs). Recent studies show that in senescent cells the intensity of such transfer increases. The research also revealed that Cdc42 and actin polymerization are indispensable for this process to occur. Here, we evaluate the hypothesis that, apart from actin and Cdc42, also IQGAP1 could be involved in direct intercellular communication. Our results showed that direct transfer occurred preferentially between senescent cells and that IQGAP1 was not essential for this process. Interestingly, cells harboring mutated IQGAP1 had altered morphology and were characterized by decreased proliferation, increased time of division and appearance of some senescence markers (increased activity of senescence-associated β-galactosidase and induction of senescence-associated secretory phenotype). Our findings suggest that IQGAP1 dysfunction can induce senescence. |
| Databáze: | OpenAIRE |
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