TY  - EJOU
AU  - Mali, Akash S. 
AU  - Das, Debanjan 
AU  - Greco, Denise 
AU  - Telensky, Petr 
AU  - Novotny, Jiri 

TI  - Opioids Promote Autophagy and Attenuate LPS-Induced Cellular Senescence-Associated Changes in Microglia
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - <b>Background:</b> Opioids can modulate mitochondrial redox homeostasis and autophagy and are implicated in the regulation of key physiological and pathological processes, including aging, cellular metabolism, and tumorigenesis. The study aimed to investigate how opioid receptor agonists influence lipopolysaccharide-induced senescence in microglia. <b>Methods:</b> C8-B4 microglial cells were either left untreated or pretreated with different opioid agonists and subsequently exposed to lipopolysaccharide (LPS). Colorimetric assays, fluorescence microscopy, flow cytometry, and Western blotting were used to assess cellular senescence, autophagy-associated changes, reactive oxygen species, and calcium levels, as well as the expression of selected marker proteins and signaling molecules. <b>Results:</b> Treatment with DAMGO, DADLE, and U-50488 significantly attenuated LPS-induced increases in intracellular calcium levels and reduced the expression of cellular senescence markers, including p53, p16, p21, SA-β-Gal activity, and mitochondrial ROS (mtROS), while enhancing total antioxidant capacity (<i>p</i> < 0.05). Notably, opioid treatment was associated with changes consistent with increased autophagy-related activity, as demonstrated by the upregulation of autophagy-related markers Autophagy-related proteins 5 and 7, beclin-1, and microtubule-associated proteins 1A/1B light chain 3B (MAP-LC3). It reversed LPS-induced impairment of autophagy-related activity, evidenced by increased degradation of p62 (<i>p</i> < 0.05). Furthermore, opioids inhibited LPS-induced activation of the phosphatidylinositol 3-kinase/Protein Kinase B/mechanistic Target of Rapamycin signaling pathway (<i>p</i> < 0.05), thereby promoting autophagy. <b>Conclusions:</b> Taken together, these findings suggest that opioids may support cell survival, attenuate LPS-associated senescence markers, and be accompanied by changes consistent with increased autophagy-related activity.
KW  - Cellular senescence; opioids; autophagy; microglia; neuroinflammation

DO  - 10.32604/biocell.2026.080886