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. 2023 Jul 22;26(8):107375. doi: 10.1016/j.isci.2023.107375

Figure 3.

Figure 3

Targeting diminished NAD+ with PARP inhibition in cells and skeletal muscle harboring polyQ-expanded AR

(A) Levels of NAD+ in quadriceps (left) and gastrocnemius (right) from WT, AR24Q, and AR100Q male mice (n = 3) at age 11 weeks.

(B) Levels of NAD+ in quadriceps (left) and gastrocnemius (right) from WT, SIRT3, AR100Q, and AR100Q-SIRT3 male mice (n = 3) at age 11 weeks.

(C) Levels of NAD+ in AR10Q-, and AR112Q-expressing PC12 cells (n = 3) treated with EtOH DHT, or DHT + olaparib (representative image from 3 experiments).

(D) ROS levels of PC12 polyQ-expanded AR112Q expressing cells (n = 12) treated with either DMSO (vehicle control), or 1 μM olaparib for 48 h (representative image from 3 experiments). ∗∗∗ = Nested two-way t-test, p ≤ 0.001.

(E) Cell death of AR100Q expressing C2C12 myotubes (n = 3) treated with either DMSO (vehicle control), or 1 μM olaparib for 10 days (representative image from 3 experiments). ∗ = Nested two-way t-test, p ≤ 0.05.

(F) Muscle mass (left) and percent of total mass (right) of gastrocnemius from WT and AR100Q male mice (n = 3) at age 8 weeks fed no-drug compounded or olaparib-compounded food.

(G) Levels of NAD+ in quadriceps (left) and gastrocnemius (right) from WT and AR100Q male mice (n = 4) at age 8 weeks fed no-drug compounded food or olaparib-compounded food.

(A–G) All statistical analysis show mean ± SD, and used a two-way ANOVA and Tukey’s post-hoc (∗ = p ≤ 0.05, ∗∗ = p ≤ 0.01, ∗∗∗ = p ≤ 0.001) unless otherwise noted. EtOH, ethanol; WT, wild type; SIRT3, SIRT3-flag overexpression; AR100Q, polyQ-expanded AR; AR100Q-SIRT3, polyQ-expanded AR with SIRT3-flag overexpression; AR10Q, non-polyQ-expanded AR; AR112Q, polyQ-expanded AR; olaparib, PARP inhibitor (1150 g of olaparib in 1 kg of feed).