Inhibition of histone deacetylase1 induces autophagy

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Abstract

Autophagy is a process where cytoplasmic materials are degraded by lysosomal machinery. Histone deacetylase (HDAC) inhibitors induce autophagy, and HDAC6, one of class II HDAC isotypes, is directly involved in autophagic degradation in the cell. However, it is unclear if class I HDAC isotype such as HDCA1 is involved in this process. To investigate if class I HDAC isotype is involved in autophagy, a specific class I HDAC inhibitor and an siRNA of HDAC1 were used to treat HeLa cells. Autophagic markers were then investigated. Both inhibition and genetic knock-down of HDAC1 in the cells significantly induced autophagic vacuole formation and lysosome function. Moreover, disruption of HDAC1 leads to the conversion of LC3-I to LC3-II. Together, these results demonstrate that HDAC1 could play a role in autophagy and specific inhibition of HDAC1 can induce autophagy.

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Materials and methods

Materials. Suberoylanilide hydroxamic acid (SAHA) was synthesized in our laboratory as described previously [9]. FK228 was kindly provided by Astellas Co, Japan. Rapamycin, monodansylcadaverine (MDC), and FITC-conjugated anti-mouse IgG were purchased from Sigma (Sigma, St. Louis, MO). All stock concentrations were made in DMSO and stored at −20 °C. Dulbecco’s modified Eagle’s medium (DMEM), antibiotics, and fetal bovine serum (FBS) were purchased from Invitrogen (Grand Island, NY). PVDF membrane

FK228 treatment induces autophagy in HeLa cells

A microbial natural product, FK228, was chosen as a small molecule probe to study the role of class I HDAC in autophagy. In order to investigate FK228 as an inducer of autophagy, we evaluated the induction of autophagosomes in FK228 treated cells by fluorescence microscopy. Autophagy mediates bulk degradation of cytoplasmic components. These components are delivered to lysosomes via autophagosomes. The microtubule-associated 1 light chain 3 (LC3), a homolog of yeast Atg8 (Aut7/Apg8), localizes

Acknowledgment

This study was supported by grants from the National R&D Program for Cancer Control, Ministry of Health & Welfare and from the Brain Korea 21 Project, Republic of Korea.

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