BLDE University Journal of Health Sciences

EDITORIAL
Year
: 2019  |  Volume : 4  |  Issue : 2  |  Page : 53--54

Hypoxia, Nobel Prize 2019 in Physiology or Medicine and Nanduri R. Prabhakar


Kusal K Das1, Shashi Bala Singh2,  
1 Department of Physiology, Shri B. M. Patil Medical College, BLDE (Deemed to be University), Vijayapur, Karnataka, India
2 Director, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana, India

Correspondence Address:
Kusal K Das
Department of Physiology, Shri B. M. Patil Medical College, BLDE (Deemed to be University), Vijayapur, Karnataka
India




How to cite this article:
Das KK, Singh SB. Hypoxia, Nobel Prize 2019 in Physiology or Medicine and Nanduri R. Prabhakar.BLDE Univ J Health Sci 2019;4:53-54


How to cite this URL:
Das KK, Singh SB. Hypoxia, Nobel Prize 2019 in Physiology or Medicine and Nanduri R. Prabhakar. BLDE Univ J Health Sci [serial online] 2019 [cited 2020 Sep 20 ];4:53-54
Available from: http://www.bldeujournalhs.in/text.asp?2019/4/2/53/275439


Full Text



The year 2019 is remarkable for hypoxia biologists as this year Nobel Prize for Physiology or Medicine has gone to three scientists. They are William G. Kaelin Jr. (Harvard University), Sir Peter J. Ratcliffe (University of Oxford), and Gregg L. Semenza (Johns Hopkins University). They have discovered how cells can sense and adapt to changing oxygen availability. They identified molecular machinery that regulates the activity of genes in response to varying levels of oxygen. Their discoveries revealed the mechanism for one of life's most essential adaptive processes. They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function by oxygen-sensing mechanisms, which allows cells to adapt their metabolism to low oxygen levels.[1]

In this regard, one man who is not included in the prestigious Nobel Prize as a winner or we can say that he missed it by a whisker is Nanduri R. Prabhakar, Ph. D., D. Sc., Harold Hines Jr. Professor of Medicine and Director, Center for Systems Biology and Oxygen Sensing, Department of Medicine, University of Chicago [Figure 1]. His discovery on mechanism of how intermittent hypoxia (IH) affects the O2-sensing mechanisms at the carotid body (CB) or on O2-regulated gene expression truly made revolution in the concept of low oxygen microenvironment in system biology. Professor Prabhakar's research redefined the concept and mechanisms of long-term effects of different patterns of IH on ventilation and blood pressure.{Figure 1}

It is well known that low oxygen microenvironment induces generation of reactive oxygen species (ROS), increased expression of p53, nuclear factor-kappa-β, associated proteins-1 AP-1, mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor-1α (HIF-1α). The increased expression of all these transcription factors leads to either cellular adaptation or cell death. The mechanisms by which mammalian cells adapt to acute and chronic alterations of oxygen tension are extremely important to understand the exact homeostasis regulation to counteract hypoxia-induced cell damage as a therapeutic strategy.[2] Prabhakar explained with evidence that IH affects hypoxic ventilatory response and increases the blood pressure also the reflexes from the CB in regulating hypoxia induced cellular mechanisms.[3] Prabhakar and Samenza describe the exact oxygen homeostasis mechanisms in relation to hypoxia-inducible factors. They postulated that oxygen delivery system is affected by the combined action of the respiratory and circulatory systems under the control of chemical and pressure receptors along with the central nervous system. It has been found that HIFs serve as master regulators to maintain oxygen homeostasis in every cell of the body by balancing O2 supply and demand.[4]

Prabhakar and Samenza (2018) explained oxygen homeostasis pathways during IH through HIF-1α- and HIF-2α-initiated ROS modulation.[5] Prabhakar's contribution in oxygen-sensing mechanisms to define the chemosensory reflex pathway mediates rapid cardiovascular and respiratory responses to acute hypoxia is also considered as great as hypoxia transcriptional factor discovery. Prabhakar explained that although HIF-1α and HIF-2α are expressed within the O2-sensing cells of the CB but HIF-1α levels are found to be lower in the CB under normoxic conditions and stimulated by IH. In case of HIF-2α levels it is found to be higher in the CB under normoxic conditions and quenched by IH.[6] Prabhakar's laboratory able to identify the long-sought oxygen sensor which works with unique critical molecule, i.e., enzyme heme oxygenase-2. The most critical explanation on fall of oxygen level with decrease in heme oxygenase-2 activity without production of carbon monoxide along with the carotid bodies instead produce abundant hydrogen sulfide by cystathionine-ϒ-lyase, which activates nerve signals. This increases respiratory rate, heart rate, and blood pressure with elevation of hydrogen sulfide and concomitant reduction of oxygen level in the system.[4]

Prabhakar has contributed immensely on CB chemoreflex in the progression of autonomic morbidities associated with cardiorespiratory diseases, such as sleep-disordered breathing with obstructive sleep apnea (OSA), congestive heart failure, and essential hypertension cannot be ignored. One of his hypotheses is that in addition to OSA, systemic hypertension may involve disturbance in the balance between HIF-1α and HIF-2α, leading to oxidative stress in the CB and adrenal medulla further leading to sympathoadrenal activation. Nanduri Prabhakar shows that adjusting the molecular signals that regulate breathing could improve treatment for sleep apnea. His research further narrates the series of signals that lead to hypertension from sleep apnea, and shows pathways to prevent it.

Hence, it is really heartbroken to most of the hypoxia researchers around the world to see one of the greatest Indian physiologists perhaps next to A. S. Paintal and Sukhamoy Lahiri missed Nobel Prize for Physiology or Medicine in 2019 by a hairsbreadth credibility with other winners. We hope Professor Prabhakar will definitely go for his greatest contribution in the future which will shape humankind in medical sciences.

References

1Press release: The Nobel Prize in Physiology or Medicine; 2019. Available from: https://www.nobelprize.org/prizes/medicine/2019/press-release/. [Last retrieved on 2019 Dec 02].
2Bagali S, Hadimani GA, Biradar MS, Das KK. Introductory chapter-primary concept of hypoxia and anoxia. In: Das KK, Biradar MS, editors. Hypoxia and Anoxia. London: InTech Open Science; 2018.
3Prabhakar NR. Oxygen sensing during intermittent hypoxia: Cellular and molecular mechanisms. J Appl Physiol (1985) 2001;90:1986-94.
4Prabhakar NR, Semenza GL. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev 2012;92:967-1003.
5Semenza GL, Prabhakar NR. The role of hypoxia-inducible factors in carotid body (patho) physiology. J Physiol 2018;596:2977-83.
6Nanduri J, Wang N, Yuan G, Khan SA, Souvannakitti D, Peng YJ, et al. Intermittent hypoxia degrades HIF-2alpha via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities. Proc Natl Acad Sci U S A 2009;106:1199-204.