• Title/Summary/Keyword: MMD I

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Deficiency of Anoctamin 5/TMEM16E causes nuclear positioning defect and impairs Ca2+ signaling of differentiated C2C12 myotubes

  • Phuong, Tam Thi Thanh;An, Jieun;Park, Sun Hwa;Kim, Ami;Choi, Hyun Bin;Kang, Tong Mook
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.539-547
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    • 2019
  • Anoctamin 5 (ANO5)/TMEM16E belongs to a member of the ANO/TMEM16 family member of anion channels. However, it is a matter of debate whether ANO5 functions as a genuine plasma membrane chloride channel. It has been recognized that mutations in the ANO5 gene cause many skeletal muscle diseases such as limb girdle muscular dystrophy type 2L (LGMD2L) and Miyoshi muscular dystrophy type 3 (MMD3) in human. However, the molecular mechanisms of the skeletal myopathies caused by ANO5 defects are poorly understood. To understand the role of ANO5 in skeletal muscle development and function, we silenced the ANO5 gene in C2C12 myoblasts and evaluated whether it impairs myogenesis and myotube function. ANO5 knockdown (ANO5-KD) by shRNA resulted in clustered or aggregated nuclei at the body of myotubes without affecting differentiation or myotube formation. Nuclear positioning defect of ANO5-KD myotubes was accompanied with reduced expression of Kif5b protein, a kinesin-related motor protein that controls nuclear transport during myogenesis. ANO5-KD impaired depolarization-induced $[Ca2^{+}]_i$ transient and reduced sarcoplasmic reticulum (SR) $Ca^{2+}$ storage. ANO5-KD resulted in reduced protein expression of the dihydropyridine receptor (DHPR) and SR $Ca^{2+}-ATPase$ subtype 1. In addition, ANO5-KD compromised co-localization between DHPR and ryanodine receptor subtype 1. It is concluded that ANO5-KD causes nuclear positioning defect by reduction of Kif5b expression, and compromises $Ca^{2+}$ signaling by downregulating the expression of DHPR and SERCA proteins.

Effects of Extracts of Folium Mori on Cadmium Aerosol Inhalation Toxicity in Rats (상엽 추출물이 흰쥐의 카드뮴 에어로졸 흡입독성에 미치는 영향)

  • Park Jae Soo;Jeung Jae Yeal;Lee Taek Jun;Kang Sung Ho;Song Young Sun;Lee Ki Nam
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.6
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    • pp.1243-1252
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    • 2002
  • To experiment the effects between cadmium inhalation toxicity and extracts of Folium Mori, rat inhalation exposure groups were exposed to cadmium aerosol in air by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cadmium concentration in the air of cadmium aerosol was 1.02㎎/㎥ and mass median diameter(MMD) was 1.40μm. Intraperitoneal injection of extracts of Folium Mori to inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were 126.39g/4 weeks and 19.18g/day from inhalation exposure group III, respectively. The highest lung and liver weight were 1.27g and 8.19g from inhalation exposure group II, respectively. The highest kidney weight was 1.805g from inhalation exposure control. The lowest cadmium content in lung was 86.39μg/g from inhalation exposure group III. The lowest cadmium concentration in blood was 7.12㎍/㎗ from inhalation exposure group III. Cadmium concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. For weekly cadmium concentration in urine, the value of the fourth week from inhalation exposure group III was the highest, 3.12㎍/㎖. For weekly cadmium concentration in feces, the value of the fourth week from inhalation exposure group III was the highest, 2.67 ㎍/g. The highest metallothionein concentration in lung was 74.65㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 386.84㎍/g from inhalation exposure group II. The highest metallothionein concentration in kidney was 236.17 ㎍/g from inhalation exposure group II.