뇌 건강해야 심장도 튼튼 Sound Mind, Strong Heart: Same Protein Sustains Both

돌연사 막으려면

존스홉킨스대 연구진, 

뇌 항우울 단백질이 심장 근육 운동에도 관여하는 사실 밝혀

경기 중 쓰러져 들것에 실려 나오는 임수혁 선수.

동아일보DB

케이콘텐츠 kcontents

지난 2000년 4월 18일. 프로야구 경기 도중 2루에 있던 주자가 갑자기 운동장에 쓰러졌다. 국가대표를 지내기도 한 전도유망한 타자는 그대로 식물인간이 되어 10년 후 하늘나라로 떠났다. 롯데자이언츠 임수혁 선수의 이야기다. 당시 임 선수를 쓰러트린 병명은 ‘부정맥’이다. 심장의 전기적인 신호에 문제가 생겨 박동이 불규칙하게 이루어지는 병을 말한다. 부정맥을 앓는 환자들은 임 선수처럼 격렬한 운동을 하면 심장 박동에 치명적인 문제가 생길 수 있다.   그런데 최근 뇌에서 학습과 기억, 항우울 기능을 담당하는 단백질이 이런 심장 질환의 원인일 수 있다는 연구 결과가 나왔다.   미국 존스홉킨스대 의대 닝 팽 박사팀은 뇌에서 학습과 기억, 항우울 기능을 담당하는 단백질이 심장 근육의 활력을 유지하는 데에도 관여한다는 사실을 밝히고 ‘미국국립과학원회보(PNAS)’ 12일자에 게재했다.   ‘뇌유래 신경영양인자(BDNF)’라고 부르는 이 단백질은 이전부터 뇌에서 학습과 기억, 항우울 기능을 담당하는 것으로 알려져 있었다. 하지만 연구진이 쥐의 심장 세포를 이용해서 실험한 결과 수축-이완운동을 하는 심장근육세포의 활력을 유지하는 데에도 중요한 역할을 한다는 사실이 밝혀졌다.   연구진은 건강한 쥐와 심부전증이 있는 쥐의 심장 세포를 시험접시에 따로 떼어 배양했다. 이 시험접시에 BDNF 단백질을 넣어 주자 정상세포들은 적극적으로 수축-이완운동을 했다. 반면 심부전증이 있는 쥐에게서 떼어낸 세포는 아무리 많은 BDNF를 넣어 줘도 전혀 반응하지 않거나 약하게 반응했다.   또 연구진은 이 결과를 바탕으로 심장세포의 표면에 존재하는 BDNF 단백질 수용체가 건강한 심장세포와 그렇지 않은 세포에서 조금 다르다는 사실 알아냈다. 이 수용체는 BDNF 단백질이 내보내는 화학신호를 세포 안으로 전달하는 역할을 한다. 단백질 수용체는 심장세포에서 생체신호를 일으키는 촉매물질을 생산하는데, 건강하지 않은 심장세포에서는 이 촉매물질이 덜 생산된다. 이 차이로 인해 BDNF 단백질 수용체가 BDNF를 잘 인식하지 못하게 되고 심장세포가 BDNF 단백질의 신호를 받아서 박동하는 능력이 떨어지게 되는 것이다. 실제로 이 수용체를 부족하게 만든 쥐를 관찰한 결과 심장의 수축-이완 기능에 이상이 있는 것으로 나타났다.   닝 팽 박사는 “격렬한 운동을 할 때 심장 기능이 악화되는 심부전증 환자들의 혈액을 분석해 보면 공통적으로 혈액 내 BDNF 단백질 농도가 낮다”며 “격렬한 운동이 심장기능 악화시키는 과정에 BDNF 단백질이 관여할 것”이라고 추정했다.   특히 이번 연구 결과는 심장과 정신 건강이 밀접하게 관련돼 있다는 것이어서 주목을 받고 있다. 보통 심장질환과 우울증을 함께 겪는 경우가 많이 있는데 BDNF 단백질이 그 이유를 설명하는 열쇠가 될 수 있기 때문이다.   연구진은 이 같은 상관관계가 사람에게서도 똑같이 나타난다면 전 세계적으로 2300만 명이 고통 받고 있는 심부전증 치료제 개발에 새로운 돌파구가 될 것으로 기대하고 있다. 동아사이언스 최영준 기자 jxabbey@donga.com

 

Newswise — A Roman philosopher was the first to note the relationship between a sound mind and a sound body. Now the findings of a new Johns Hopkins study reveal a possible biochemical explanation behind this ancient observation. The research, published ahead of print Jan. 12 in the Proceedings of the National Academy of Sciences, reveals that a protein already known to act as a natural antidepressant, enhance learning and memory, power nerve cell growth, and nourish blood vessels is also a central player in maintaining heart muscle vitality. The team’s experiments, conducted in mice and lab-grown heart cells, show this multi-tasking protein, a nerve-growth factor called BDNF (brain-derived neurotrophic factor), helps sustain the ability of heart muscle cells to contract and relax properly. The results reveal that either BDNF deficiency or cell insensitivity to BDNF’s presence can precipitate heart muscle dysfunction, particularly under conditions of chronic or repeated physical stress on the heart, such as endurance training or high blood pressure. Specifically, the researchers tracked BDNF’s role in a cascade of molecular signaling events in heart cells, the disruption of which led to heart muscle failure. If confirmed in humans, the research team says, the findings could pave the way to new treatments for certain forms of heart failure, a disorder that affects nearly 6 million Americans and more than 23 million people worldwide. In addition, because of BDNF’s well-known antidepressant effects and its role as a booster of nerve cell health, the research teams says the results suggest a possible biochemical link between depression and heart disease, two disorders that tend to occur in concert but whose relationship remains poorly understood. “Our results are not only a vivid reminder of the astounding complexity of the heart’s chemistry and physiology, but also a striking example of the ability of a single protein to act on multiple fronts and affect many organs and functions,” says lead investigator Ning Feng, M.D., Ph.D., a cardiology fellow at the Johns Hopkins University School of Medicine. The findings also can help clarify the biological means behind recent — and unexplained observations — that heart failure patients whose cardiac function worsens during physical exertion have low levels of BDNF in the blood. “Our observation that BDNF directly controls the ability of heart muscle cells to ‘beat’ properly offers one possible explanation behind the declining cardiac function seen in people with heart failure, especially during exercise,” says senior author Nazareno Paolocci, M.D., Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine. In an initial set of experiments, the scientists isolated cardiac cells from rodents with either normal or failing hearts in a lab dish and exposed the cells to BDNF. The normal heart cells responded by contracting and relaxing vigorously in the presence of BDNF, a phenomenon marked by peaks of contraction-triggering calcium flow into the cells. However, cells obtained from failing hearts, even when awash in BDNF, responded weakly or not at all. To determine why, the team homed in on BDNF’s receptor, a molecule called TrkB, located on the surface of cells and responsible for receiving BDNF’s chemical signals and transmitting them inside the cell. Compared with cardiac cells from mice with normal hearts, the failing heart cells had a slightly different version of the TrkB receptor, one that produces less of a catalyst protein responsible for triggering critical signaling inside the cardiac cell. This slightly sub-performing version of the receptor was less responsive to BDNF, rendering the heart cell less sensitive to it. While this TrkB variant is fairly common and does not necessarily portend disease, it may render the heart cells of those who carry the altered version less capable of using BDNF, the researchers say. Mice engineered to lack TrkB receptors in their heart cells developed impaired cardiac function. Their hearts contracted poorly, pumped blood less efficiently and took longer to relax after each beat. “Taken together, these findings show that any abnormality in the way BDNF communicates with its receptor appears to unlock a cascade of chemical glitches that eventually leads to poor cardiac function,” Feng says. The investigators say that disruptions in proper BDNF-TrkB signaling can even explain what drives chemotherapy-induced heart failure, a serious and well-established side effect of certain cancer treatments. Such treatments include chemicals that block multiple growth-factor receptors, TrkB among them, to halt tumor growth. And while this approach is critical to stave off cancer progression, it can also inadvertently lead to heart failure by interfering with the ability of cardiac cells to respond to the BDNF circulating in the body. Another important finding, the researchers say, is that mice with missing BDNF receptors remained sensitive to adrenaline, the neurotransmitter released during fight-or-flight situations to infuse the heart with extra energy needed for peak cardiac performance during bouts of intense physical or emotional activity. The finding, the scientists say, means that BDNF affects cardiac function independently and separately from adrenaline by providing continuous, low-level fuel for heart contraction under normal conditions or prolonged periods of slightly elevated cardiac output, such as endurance training. “Just like a constant low flame can keep a pot on slow simmer, constant levels of BDNF seem to maintain heart muscle vitality,” Paolocci says.  The researchers point out that low levels of BDNF by themselves may not be enough to cause immediate heart disease, but chronic BDNF deficiency or insensitivity, compounded by additional physiologic or pathologic stressors, is a main culprit in fueling the disease. “In the absence of chronic stressors, such as hypertension or an elevated workload of the heart muscle, BDNF deficiency may not cause full-blown disease, but it could be the proverbial straw that leads to a ‘broken heart,’” Paolocci says. The research was funded in part by the American Heart Association under grant number GRNT17070027 and by the National Institutes of Health under grant number T32HL-0227, with additional funding support from the Magic That Matters Fund of the Division of Cardiology at Johns Hopkins. Other investigators involved in the research included Sabine Huke, Guangshuo Zhu, Carlo Tocchetti, Sa Shi, Takeshi Aiba, Nina Kaludercic, Donald Hoover, Sarah Beck, Joseph Mankowski, Gordon Tomaselli, Donald Bers and David Kass. http://www.newswise.com/articles/sound-mind-strong-heart-same-protein-sustains-both

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