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. 2020 Oct 14;21(20):7608.
doi: 10.3390/ijms21207608.

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

Piotr Karabowicz  1 , Adam Wroński  2 , Halina Ostrowska  3 , Georg Waeg  4 , Neven Zarkovic  5 , Elżbieta Skrzydlewska  1
Affiliations

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

Piotr Karabowicz et al. Int J Mol Sci. .

Abstract

Psoriasis is a skin disease that is accompanied by oxidative stress resulting in modification of cell components, including proteins. Therefore, we investigated the relationship between the intensity of oxidative stress and the expression and activity of the proteasomal system as well as autophagy, responsible for the degradation of oxidatively modified proteins in the blood cells of patients with psoriasis. Our results showed that the caspase-like, trypsin-like, and chymotrypsin-like activity of the 20S proteasome in lymphocytes, erythrocytes, and granulocytes was lower, while the expression of constitutive proteasome and immunoproteasome subunits in lymphocytes was increased cells of psoriatic patients compared to healthy subjects. Conversely, the expression of constitutive subunits in erythrocytes, and both constitutive and immunoproteasomal subunits in granulocytes were reduced. However, a significant increase in the autophagy flux (assessed using LC3BII/LC3BI ratio) independent of the AKT pathway was observed. The levels of 4-HNE, 4-HNE-protein adducts, and proteins carbonyl groups were significantly higher in the blood cells of psoriatic patients. The decreased activity of the 20S proteasome together with the increased autophagy and the significantly increased level of proteins carbonyl groups and 4-HNE-protein adducts indicate a proteostatic imbalance in the blood cells of patients with psoriasis.

Keywords: autophagy; immunoproteasomal subunits; oxidative stress; proteasomal activity; psoriasis.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
(A) Expression of the constitutive proteasome (β1, β2, β5) and immunoproteasome (β1i, β2i, β5i) subunits in lymphocytes from patients with psoriasis (n = 6), in comparison to healthy subjects (control), (n = 6). (B) Caspase-like (Cas-L), trypsin-like (T-L), and chymotrypsin-like (ChT-L) activities of the proteasomes in lymphocytes from patients with psoriasis (n = 16) and healthy subjects (control), (n = 12). Values in (A) and (B) are expressed as a percentage of control. ∗—statistical significance at p < 0.05 vs. control.
Figure 2
Figure 2
(A) Expression of the constitutive proteasome (β1, β2, β5) and immunoproteasome (β1i, β2i, β5i) subunits in granulocytes from patients with psoriasis (n = 6), in comparison to healthy subjects (control), (n = 6). (B) Caspase-like (Cas-L), trypsin-like (T-L), and chymotrypsin-like (ChT-L) activities of the proteasomes in granulocytes from patients with psoriasis (n = 16) and healthy subjects (control), (n = 12). Values in (A) and (B) are expressed as a percentage of control. ∗—statistical significance at p < 0.05 vs. control.
Figure 3
Figure 3
(A) Expression of the constitutive proteasome (β1, β2, β5) and immunoproteasome (β1i, β2i, β5i) subunits in erythrocytes from patients with psoriasis (n = 6), in comparison to healthy subjects (control), (n = 6). (B) Caspase-like (Cas-L), trypsin-like (T-L), and chymotrypsin-like (ChT-L) activities of the proteasomes in erythrocytes from patients with psoriasis (n = 16) and healthy subjects (control), (n = 12). Values in (A) and (B) are expressed as a percentage of control. ∗—statistical significance at p < 0.05 vs. control.
Figure 4
Figure 4
The ratio of LC3BII/LC3BI expression in lymphocytes (L), erythrocytes (E), and granulocytes (G) from psoriatic patients (n = 6), in comparison to healthy subjects (control), (n = 6). Values are expressed as a percentage of control. ∗—statistical significance at p < 0.05 vs. control.
Figure 5
Figure 5
Phosphorylated AKT (pAKT)/AKT expression ratio in lymphocytes (L), erythrocytes (E), and granulocytes (G) from psoriatic patients (n = 6), in comparison to healthy subjects (control), (n = 6). Values are expressed as a percentage of control. ∗—statistical significance at p < 0.05 vs. control.
Figure 6
Figure 6
The level of 4-HNE (A), 4-HNE-protein adducts (B), and carbonylated proteins (C) in erythrocytes (E, n = 68), lymphocytes (L, n = 20), and granulocytes (G, n = 20) of psoriatic patients compared to healthy subjects (control) (E, n = 34, L, n = 10, and G, n = 10); ∗—statistical significance at p < 0.05 vs. control.
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