HDAC7 modulates TNF-α-mediated suppression of Leydig cell steroidogenesis.
The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) has an inhibitory role in gonadal functions particularly in the steroidogenesis of Leydig cells. In the present study, we demonstrate that TNF-α activates histone deacetylases 7 (HDAC7), which regulates the expression of steroidogenic enzyme genes in Leydig cells. LC-540 Leydig cells were treated with TNF-α (10 ng/ml) for different time intervals. TNF-α treatment significantly suppressed histone H3 acetylation and methylation and, concomitantly, increased the total histone deacetylases activity in LC-540 Leydig cells. RT-PCR and western blot analysis revealed that HDAC7 was up-regulated in TNF-α-treated cells. Our results also demonstrated that an siRNA-mediated knockdown of HDAC7 restores the expression of steroidogenic proteins in TNF-α-treated Leydig cells. These findings provide valuable information that TNF-α-mediated suppression of steroidogenesis involves HDAC7 in Leydig cells.
Department of Biochemistry, Bharathidasan University, Tiruchirappalli, 620 024, India.
Mohanraj
M
Sadasivam
Balamurugan
B
Ramatchandirin
Sivasangari
S
Balakrishnan
Chidambaram
C
Prahalathan
D000107:Acetylation; D000818:Animals; D053898:Biosynthetic Pathways; D002460:Cell Line; D004790:Enzyme Induction; D006655:Histone Deacetylases / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D007985:Leydig Cells / Q000201:enzymology*; D008297:Male; D008745:Methylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D013256:Steroids / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D006657:Histones; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; C000606948:HDAC7 protein, rat; D006655:Histone Deacetylases