Association between the mitochondrial DNA 4977 common deletion in the hair shaft and hearing loss in presbycusis

AbstractScar formation as a result of corneal wound healing is a leading cause of blindness. It is a challenge to understand why scar formation is more likely to occur in the central part of the cornea as compared to the peripheral part. The purpose of this study was to unravel the underlying mechanisms. We applied RNA-seq to uncover the differences of expression profile in keratocytes in the central/peripheral part of the cornea. The relative quantity of mitochondrial RNA was measured by multiplex qPCR. The characterization of mitochondrial RNA in the cytoplasm was confirmed by immunofluoresence microscope and biochemical approach. Gene expression was analyzed by western blot and RT qPCR. We demonstrate that the occurrence of mitochondrial DNA common deletion is greater in keratocytes from the central cornea as compared to those of the peripheral part. The keratocytes with CD have elevated oxidative stress levels, which leads to the leakage of mitochondrial double-stranded RNA into the cytoplasm. The cytoplasmic mitochondrial double-stranded RNA is sensed by MDA5, which induces NF-κB activation. The NF-κB activation thereafter induces fibrosis-like extracellular matrix expressions and IL-8 mRNA transcription. These results provide a novel explanation of the different clinical outcome in different regions of the cornea during wound healing.

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Analysis of Common Deletion (CD) and a novel deletion of mitochondrial DNA induced by ionizing radiation

International Journal of Radiation Biology ◽

10.1080/09553000701370878 ◽

2007 ◽

Vol 83 (7) ◽

pp. 433-442 ◽

Cited By ~ 34

Author(s):

Lu Wang ◽

Yoshikazu Kuwahara ◽

Li Li ◽

Taisuke Baba ◽

Ryong-Woon Shin ◽

...

Keyword(s):

Mitochondrial Dna ◽

Ionizing Radiation ◽

Common Deletion

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The A1555G mitochondrial DNA mutation in Greek patients with non-syndromic, sensorineural hearing loss

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2009.10.044 ◽

2009 ◽

Vol 390 (3) ◽

pp. 755-757 ◽

Cited By ~ 7

Author(s):

Haris Kokotas ◽

Maria Grigoriadou ◽

George S. Korres ◽

Elisabeth Ferekidou ◽

Eleftheria Papadopoulou ◽

...

Keyword(s):

Hearing Loss ◽

Mitochondrial Dna ◽

Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Mitochondrial Dna Mutation ◽

Dna Mutation

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Audiological Features and Mitochondrial DNA Sequence in a Large Family Carrying Mitochondrial A1555G Mutation without Use of Aminoglycoside

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940511400213 ◽

2005 ◽

Vol 114 (2) ◽

pp. 153-160 ◽

Cited By ~ 12

Author(s):

Tatsuo Matsunaga ◽

Hiroshi Kumanomido ◽

Yu-ichi Goto ◽

Masae Shiroma ◽

Shin-ichi Usami

Keyword(s):

Hearing Loss ◽

Mitochondrial Dna ◽

Dna Sequences ◽

Large Family ◽

Outer Hair Cells ◽

Japanese Family ◽

A1555g Mutation ◽

Genetic Mechanisms ◽

High Degree ◽

Sibling Group

To elucidate the pathophysiological and genetic mechanisms of hearing loss associated with the homoplasmic mitochondrial A1555G mutation in the absence of aminoglycoside exposure, we conducted audiological and genetic analyses on 67 maternally related members of a large Japanese family carrying this mutation. A consistent pattern was evident in the audiograms, with features of sensory presbycusis, cochlear origin at all levels of hearing loss, and a high degree of vulnerability of outer hair cells. That the degree of hearing loss was similar in affected subjects within the same sibling group but differed between sibling groups suggests the involvement of nuclear modifier genes. Total mitochondrial DNA sequences were completely identical among subjects with various levels of hearing loss, and lacked additional pathogenic mutations. For the diagnosis of sensorineural hearing loss, the mitochondrial A1555G mutation should be considered when these features are present even in the absence of aminoglycoside exposure.

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Oxidation‐ or Radiation‐Derived Effects on Human Mitochondria as Seen in a Fibroblast Cell Line Derived from a Family Known to Have Elevated Levels of the 4977‐bp Common Deletion in its Mitochondrial DNA

The FASEB Journal ◽

10.1096/fasebj.24.1_supplement.510.7 ◽

2010 ◽

Vol 24 (S1) ◽

Author(s):

Zachary Stoll ◽

Wendy Pogozelski

Keyword(s):

Mitochondrial Dna ◽

Cell Line ◽

Fibroblast Cell ◽

Fibroblast Cell Line ◽

Common Deletion

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Mitochondrial DNA 4977-base pair common deletion in blood leukocytes and melanoma risk

Pigment Cell & Melanoma Research ◽

10.1111/pcmr.12474 ◽

2016 ◽

Vol 29 (3) ◽

pp. 372-378 ◽

Cited By ~ 3

Author(s):

Jie Shen ◽

Jie Wan ◽

Chad Huff ◽

Shenying Fang ◽

Jeffrey E. Lee ◽

...

Keyword(s):

Mitochondrial Dna ◽

Base Pair ◽

Melanoma Risk ◽

Blood Leukocytes ◽

Common Deletion

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Common Deletion (CD) in mitochondrial DNA of irradiated rat heart

Anais da Academia Brasileira de Ciências ◽

10.1590/0001-37652014110912 ◽

2014 ◽

Vol 86 (2) ◽

pp. 685-694 ◽

Cited By ~ 1

Author(s):

RAQUEL G. SIQUEIRA ◽

DAYSE A. DA SILVA ◽

LUIZ D.B. DE MELO ◽

ELIZEU F. DE CARVALHO ◽

SAMARA C. FERREIRA-MACHADO ◽

...

Keyword(s):

Mitochondrial Dna ◽

Ionizing Radiation ◽

Real Time ◽

Real Time Pcr ◽

Rat Heart ◽

Wistar Rats ◽

Post Irradiation ◽

Male Wistar Rats ◽

The Common ◽

Common Deletion

The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rduntil the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels.

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