노화에 따른 근세포 내 산화환원 관련 철분축적과 근세포 내 단백질 산화손상과의 관련성
Relationship of Age-Associated Accumulation of Intracellular Iron with Protein Oxidative Damages in Skeletal Muscle of Rats
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노화에 따른 인체 내 free radicals 축척은 골격근 세포손상을 촉진, 노화과정에서 골격근 감소에 따른 sarcopenia를 증가시키는 중요 인자로 보고되었다. 하지만 sarcopenia를 설명하는 free radical 이론에서 중요한 역할을 갖는 철분 중 산화환원반응과 관련성이 높은 철분형태의 세포내 총량과 근세포의 단백질 산화손상과의 관련성 규명이 필요하다. 본 연구는 Fisher-344 쥐 모델(n = 10/group)을 이용해 노화에 의한 골격근 세포내 단백질 산화손상정도와 산화환원반응과 관련성이 높다고 보고된 3가지 철분형태의 근세포내 총량과 골격근 세포내 단백질 농도 등을 측정하여 다음과 같은 결과를 얻었다. 본 연구는 Old(25개월)와 Young(6개월) 집단간 비교시, 근량과 근세포내 단백질농도는 Old집단에서 각각 -3%, -11%씩 낮게 나왔으며 산화환원반응과 관련있는 철분의 근세포내 총량은 137% 증가하였지만, 모두 통계적 유의함은 검증되지 않았다. 산화환원반응과 관련있는 철분의 근세포내 총량은 단백질산화손상의 정도와 순상관관계(r = 0.34)를 보였지만 통계적 유의함은 검증되지 않았으며, 근세포 단백질 농도와는 통계적으로 유의한 역상관관계(r = 0.83, p < 0.0001)를 보였다. 결론적으로, 비록 산화환원반응과 관련있는 철분의 근세포내 총량과 단백질 산화손상간 순상관관계가 통계적으로 유의한 차이를 보이지 않았지만, 이러한 철분형태의 총량과 근세포 단백질 농도간의 통계적으로 유의하게 높은 역상관관계는 세포내 철분 축적이 골격근 노화기전을 이해함에 중요한 의미를 부여한다고 사료된다. 하지만 본 연구에서 제시하는 이러한 상관관계는 더 많은 사후 연구들을 통해서 인과관계를 밝혀내야 할 것이다.
Abstract
Intracellular iron plays a critical role in oxidative stress and is accumulating in a variety of different tissues with aging. However, no study has investigated a relationship of intracellular iron concentration with levels of oxidative damages to protein and lipid in skeletal muscles. Therefore, the purpose of this study was to investigate a relationship of intracellular iron with oxidative damage and age-associated changes in muscle mass in plantaris by comparing young (6 months old) and old (25 months old) male Fisher-344 rats (n=10/group). Our study showed age-associated declines in muscle mass (-3%) and protein concentration (-11%), but no statistically significant difference was detected (p > 0.05). Total intracellular iron concentration is 137% increased with age, but no statistically significant difference was detected (p = 0.073). Our data show no statistically significant correlation of intracellular iron concentration with levels of oxidative damages to cellular proteins in skeletal muscles, although the level of oxidative damages to protein is increased with concentrations of total irons (r = 0.34). However, the concentration of intracellular iron is highly, significantly correlated with the intracellular protein concentration in skeletal muscle (r = 0.83, p < 0.0001). In conclusion, although a positive correlation between intracellular iron concentration and the level of protein oxidative damage is not statistically significant, it is clear that intracellular iron concentration is strongly, negatively correlated with intracellular protein concentration which is decreased with aging.
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