Aripiprazole, but Not Olanzapine, Alters the Response to Oxida-Tive Stress, Reducing the Activation of Mitogen-Activated Protein Kinases (MAPKs) and Promoting Cell Survival in FAO Cells DOI Open Access
Barbara Kramar, Tinkara Pirc Marolt, Ayşe Mine Yılmaz

et al.

Published: July 2, 2024

Chronic administration of atypical antipsychotics (AAPs) is commonly associated with in-creased cardiovascular disease load. Although the increase in weight gain and related dis-ease risk generally considered main contributing factor, direct interference mi-tochondrial bioenergetics, particularly liver, where these drugs are catabolized, emerging as an additional relevant contributor to metabolic that needs be considered. In this study, we compared effects two AAPs disparate profiles, olanzapine (OLA), which obesogenic, aripiprazole (ARI), not, on response Fao cells oxidative stress. We found treated ARI sur-vive better a challenge H2O2 while OLA treatment has opposite effect. This en-hanced survival not reduction apoptosis rate. fact, display higher apoptotic rates than control exposed H2O2. Gene expression analysis pro anti-apoptotic factors revealed changes induced by were dampened cells, but suggesting reduced respon-siveness stimuli, notion was consistent activation MAPK STAT3 phosphorylation H2O2, enhanced their re-sponse Loss stress elevation mitochondrial production O2•-, known desensitizing factor. The physiological rele-vance increased O2•- further supported observed mitophagy flux likely mitochon-drial damage. An finding protected pro-teasome activity effect possibly preservation signaling function cells. sum, study highlights underlying alterations cell physiology derived from inter-ference function, de-sensitize signaling,

Language: Английский

Aripiprazole, but Not Olanzapine, Alters the Response to Oxida-Tive Stress, Reducing the Activation of Mitogen-Activated Protein Kinases (MAPKs) and Promoting Cell Survival in FAO Cells DOI Open Access
Barbara Kramar, Tinkara Pirc Marolt, Ayşe Mine Yılmaz

et al.

Published: July 2, 2024

Chronic administration of atypical antipsychotics (AAPs) is commonly associated with in-creased cardiovascular disease load. Although the increase in weight gain and related dis-ease risk generally considered main contributing factor, direct interference mi-tochondrial bioenergetics, particularly liver, where these drugs are catabolized, emerging as an additional relevant contributor to metabolic that needs be considered. In this study, we compared effects two AAPs disparate profiles, olanzapine (OLA), which obesogenic, aripiprazole (ARI), not, on response Fao cells oxidative stress. We found treated ARI sur-vive better a challenge H2O2 while OLA treatment has opposite effect. This en-hanced survival not reduction apoptosis rate. fact, display higher apoptotic rates than control exposed H2O2. Gene expression analysis pro anti-apoptotic factors revealed changes induced by were dampened cells, but suggesting reduced respon-siveness stimuli, notion was consistent activation MAPK STAT3 phosphorylation H2O2, enhanced their re-sponse Loss stress elevation mitochondrial production O2•-, known desensitizing factor. The physiological rele-vance increased O2•- further supported observed mitophagy flux likely mitochon-drial damage. An finding protected pro-teasome activity effect possibly preservation signaling function cells. sum, study highlights underlying alterations cell physiology derived from inter-ference function, de-sensitize signaling,

Language: Английский

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