The LKB1-AMPK-{alpha}1 signaling pathway triggers hypoxic pulmonary vasoconstriction downstream of mitochondria

Hypoxic pulmonary vasoconstriction (HPV), which aids ventilation-perfusion matching in the lungs, is triggered by mechanisms intrinsic to pulmonary arterial smooth muscles. The unique sensitivity of these muscles to hypoxia is conferred by mitochondrial cytochrome c oxidase subunit 4 isoform 2, the inhibition of which has been proposed to trigger HPV through increased generation of mitochondrial reactive oxygen species. Contrary to this model, we have shown that the LKB1–AMPK-α1 signaling pathway is critical to HPV. Spectral Doppler ultrasound revealed that deletion of the AMPK-α1 catalytic subunit blocked HPV in mice during mild (8% O2) and severe (5% O2) hypoxia, whereas AMPK-α2 deletion attenuated HPV only during severe hypoxia. By contrast, neither of these genetic manipulations affected serotonin-induced reductions in pulmonary vascular flow. HPV was also attenuated by reduced expression of LKB1, a kinase that activates AMPK during energy stress, but not after deletion of CaMKK2, a kinase that activates AMPK in response to increases in cytoplasmic Ca2+. Fluorescence imaging of acutely isolated pulmonary arterial myocytes revealed that AMPK-α1 or AMPK-α2 deletion did not affect mitochondrial membrane potential during normoxia or hypoxia. However, deletion of AMPK-α1, but not of AMPK-α2, blocked hypoxia from inhibiting KV1.5, the classical "oxygen-sensing" K+ channel in pulmonary arterial myocytes. We conclude that ...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

Related Links:

The National Institutes of Health (NIH) would receive $34.4 billion in FY 2020, roughly $4.7 billion or 13 percent below the levels enacted by Congress for FY 2019, according to the President’s Budget released on March 11. The budget for NIH includes $492 million in funding made available through the 21st Century Cures Act and $150 million in mandatory funding. The leading biomedical research agency in the world would receive budget cuts across the board. All NIH centers are slated for budget reductions: National Cancer Institute: -8.7 percent National Heart, Lung, and Blood Institute: -14 percent National Inst...
Source: Public Policy Reports - Category: Biology Authors: Source Type: news
Resumo O artigo pretende identificar e analisar criticamente, com base no quadro anal ítico do conceito de vulnerabilidade, estudos qualitativos sobre a vulnerabilidade de caminhoneiros ao HIV. Os critérios de inclusão foram: abordar a temática da susceptibilidade dos caminhoneiros ao HIV/AIDS e empregar a abordagem qualitativa. Foram encontrados 445 resumos, dentre os quais 17 a rtigos foram incluídos na análise e categorizados em “ estudos socioculturais ” , “ estudos avaliativos ” e “ estudos de comportamentos de risco ” . A an álise fo...
Source: Ciencia e Saude Coletiva - Category: Occupational Health Source Type: research
The administration will focus on more than 50 “ hot spots ” in the U.S. that annually account for half of new H.I.V. infections. A clinic in the Deep South sees the challenges every day.
Source: NYT Health - Category: Consumer Health News Authors: Tags: Acquired Immune Deficiency Syndrome Blacks Homosexuality and Bisexuality Drugs (Pharmaceuticals) Federal Budget (US) Epidemics United States Politics and Government Medicaid Source Type: news
CONCLUSIONS: Sociodemographic factors and HIV/AIDS-related aspects were influential in the QoL of people living with HIV/AIDS.
Source: Revista da Sociedade Brasileira de Medicina Tropical - Category: Tropical Medicine Source Type: research
Dr Amy Faith Ho demonstrates four important, if uncommon, intubation techniques, with visual aids.Medscape Emergency Medicine
Source: Medscape Emergency Medicine Headlines - Category: Emergency Medicine Tags: Emergency Medicine Commentary Source Type: news
Canada privatized its air traffic control (ATC) system in 1996. Today, Nav Canada is on the leading edge of ATC innovation worldwide. With Iridium, Nav Canada co-foundedAerion in 2012, which produces satellite-based tracking of global airliner movements. This is the future of air traffic control as it promises greater safety, fewer delays, savings of fuel, and more efficient use of airspace. The U.S. ATC system is not an investor in this revolutionary project.Our government-run ATC is falling behind the privatized systems in Canada and the United Kingdom. ATC is a high-tech business, yet we run our system as anold-fashione...
Source: Cato-at-liberty - Category: American Health Authors: Source Type: blogs
Overall, 92.8 percent of oral solid medications contain at least one potential allergen
Source: The Doctors Lounge - Psychiatry - Category: Psychiatry Tags: Cardiology, Dermatology, Endocrinology, Family Medicine, Geriatrics, Gastroenterology, Gynecology, Infections, AIDS, Internal Medicine, Allergy, Critical Care, Emergency Medicine, Nephrology, Neurology, Nursing, Oncology, Ophthalmology, Orthopedics, ENT, Source Type: news
Funding Opportunity PAR-19-223 from the NIH Guide for Grants and Contracts. Avenir means future in French, and this award looks toward the future by supporting early stage investigators proposing highly innovative studies. The award will support those in an early stage of their career who may lack the preliminary data required for an R01 grant, but who propose high impact research and who show promise of being tomorrow's leaders in the field. NIDA has developed two Avenir Award Programs, one for HIV/AIDS research and the other for genetics or epigenetics studies.
Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
MONDAY, March 18, 2019 -- Shortfalls in HIV testing and treatment are hampering efforts to stop new infections of the AIDS-causing virus in the United States, the Centers for Disease Control and Prevention says. " We have the tools to end the HIV...
Source: - Daily MedNews - Category: General Medicine Source Type: news
No abstract available
Source: AIDS - Category: Infectious Diseases Tags: NOTES AND QUOTES Source Type: research
More News: Environmental Health | Genetics | HIV AIDS | Mitochondria | Perfusion | Science | Ultrasound