Effects of obesity on protein kinase C, brain creatine kinase, transcription, and autophagy in cochlea
- 267 Downloads
Diet-induced obesity (DIO) has been shown to exacerbate hearing degeneration via increased hypoxia, inflammatory responses, and cell loss via both caspase-dependent and caspase-independent apoptosis signaling pathways. This study aimed to investigate the effects of DIO on the mRNA expressions of protein kinase c-β (PKC-β), brain creatine kinase (CKB), transcription modification genes, and autophagy-related genes in the cochlea of CD/1 mice. Sixteen 4-week-old male CD/1 mice were randomly divided into 2 groups. For 16 weeks, the DIO group was fed a high fat diet (60% kcal fat) and the controls were fed a standard diet. Morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared. Results showed that body weight, body length, body-mass index, omental fat, plasma triglyceride, and auditory brainstem response thresholds were significantly elevated in the DIO group compared with those of the control group. The ratio of vessel wall thickness to radius in the stria vascularis was significantly higher in the DIO group. The cell densities in the spiral ganglion, but not in the spiral prominence, of the cochlea were significantly lower in the DIO group. The expression of histone deacetylation gene 1 (HDAC1) was significantly higher in the DIO group than the control group. However, the expressions of PKC-β, CKB, HDAC3, histone acetyltransferase gene (P300), lysosome-associated membrane protein 2 (Lamp2), and light chain 3 (Lc3) genes were not significantly different between two groups. These results suggest that DIO might exacerbate hearing degeneration possibly via increased HDAC1 gene expression in the cochlea of CD/1 mice.
KeywordsObesity Protein kinase C Brain creatine kinase Transcription Autophagy Cochlea
Compliance with ethical standards
This project was supported by grant DTCRD-99-I-07 and DTCRD-99-2-E-01.
The authors have no conflicts of interest to declare.
- Choi KC, Park S, Lim BJ, Seong AR, Lee YH, Shiota M, Yokomizo A, Naito S, Na Y, Yoon HG (2011) Procyanidin B3, an inhibitor of histone acetyltransferase, enhances the action of antagonist for prostate cancer cells via inhibition of p300-dependent acetylation of androgen receptor. Biochem J 433:235–244CrossRefPubMedGoogle Scholar
- Fransen E, Topsakal V, Hendrickx JJ, Van Laer L, Huyghe JR, Van Eyken E, Lemkens N, Hannula S, Mäki-Torkko E, Jensen M, Demeester K, Tropitzsch A, Bonaconsa A, Mazzoli M, Espeso A, Verbruggen K, Huyghe J, Huygen PL, Kunst S, Manninen M, Diaz-Lacava A, Steffens M, Wienker TF, Pyykkö I, Cremers CW, Kremer H, Dhooge I, Stephens D, Orzan E, Pfister M, Bille M, Parving A, Sorri M, Van de Heyning P, Van Camp G (2008) Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective: A European Population-based Multicenter Study. J Assoc Res Otolaryngol 9:264–276CrossRefPubMedPubMedCentralGoogle Scholar
- Mima A, Ohshiro Y, Kitada M, Matsumoto M, Geraldes P, Li C, Li Q, White GS, Cahill C, Rask-Madsen C, King GL (2011) Glomerular-specific protein kinase C-β-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity. Kidney Int 79(8):883–896CrossRefPubMedPubMedCentralGoogle Scholar
- Santer FR, Höschele PP, Oh SJ, Erb HH, Bouchal J, Carvarretta IT, Parson W, Meyers DJ, Cole PA, Culig Z (2012) Inhibition of the acetyltransferases p300 and CBP reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Mol Cancer Ther 1158:1535–7163Google Scholar
- Senese S, Zaragoza K, Minardi S, Muradore I, Ronzoni S, Passafaro A, Bernard L, Draetta GF, Alcalay M, Seiser C, Chiocca S (2007) Role for histone deacetylase 1 in human tumor cell proliferation. Mol Cell Biol 4784–4795Google Scholar
- Tadros SF, D'Souza M, Zhu X, Frisina RD (2014) Age-related gene expression changes for antioxidants in the CBA mouse cochlea. PLoS One 9(e90279):1–9Google Scholar
- Waltregny D, North B, Van Mellaert F, de Leval J, Verdin E, Castronovo V (2004) Screening of histone deacetylases (HDAC) expression in human prostate cancer reveals distinct class I HDAC profiles between epithelial and sromal cells. Eur J Histochem 3:273–290Google Scholar