|
Originally published In Press as doi:10.1074/jbc.M002950200 on June 28, 2000
J. Biol. Chem., Vol. 275, Issue 36, 27838-27844, September 8, 2000
Ouabain Interaction with Cardiac
Na+/K+-ATPase Initiates Signal Cascades
Independent of Changes in Intracellular Na+ and
Ca2+ Concentrations*
Jiang
Liu ,
Jiang
Tian ,
Michael
Haas ,
Joseph I.
Shapiro§,
Amir
Askari , and
Zijian
Xie ¶
From the Departments of Pharmacology and
§ Medicine, Medical College of Ohio, Toledo, Ohio
43614
We have shown previously that partial inhibition
of the cardiac myocyte Na+/K+-ATPase
activates signal pathways that regulate myocyte growth and
growth-related genes and that increases in intracellular
Ca2+ concentration ([Ca2+]i) and
reactive oxygen species (ROS) are two essential second messengers
within these pathways. The aim of this work was to explore the relation
between [Ca2+]i and ROS. When myocytes were in a
Ca2+-free medium, ouabain caused no change in
[Ca2+]i, but it increased ROS as it did when the
cells were in a Ca2+-containing medium. Ouabain-induced
increase in ROS also occurred under conditions where there was little
or no change in [Na+]i. Exposure of myocytes in
Ca2+-free medium to monensin did not increase ROS. Increase
in protein tyrosine phosphorylation, an early event induced by ouabain,
was also independent of changes in [Ca2+]i and
[Na+]i. Ouabain-induced generation of ROS in
myocytes was antagonized by genistein, a dominant negative Ras, and
myxothiazol/diphenyleneiodonium, indicating a mitochondrial origin for
the Ras-dependent ROS generation. These findings, along
with our previous data, indicate that increases in
[Ca2+]i and ROS in cardiac myocytes are induced
by two parallel pathways initiated at the plasma membrane: One being
the ouabain-altered transient interactions of a fraction of the
Na+/K+-ATPase with neighboring proteins (Src,
growth factor receptors, adaptor proteins, and Ras) leading to ROS
generation, and the other, inhibition of the transport function of
another fraction of the Na+/K+-ATPase leading
to rise in [Ca2+]i. Evidently, the gene
regulatory effects of ouabain in cardiac myocytes require the
downstream collaborations of ROS and
[Ca2+]i.
*
This work was supported by Grants HL-36573 and HL-63238
awarded by the NHLBI, National Institutes of Health, United
States Public Health Service, Department of Health and Human Services.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed: Dept. of
Pharmacology, Medical College of Ohio, 3035 Arlington Ave., Toledo, OH 43614-5804. Tel.: 419-383-4182; Fax: 419-383-2871; E-mail:
mheck@mco.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
L. Wang, A. T. Dennis, P. Trieu, F. Charron, N. Ethier, T. E. Hebert, X. Wan, and E. Ficker
Intracellular Potassium Stabilizes Human Ether-a-go-go-Related Gene Channels for Export from Endoplasmic Reticulum
Mol. Pharmacol.,
April 1, 2009;
75(4):
927 - 937.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Y. Bagrov, J. I. Shapiro, and O. V. Fedorova
Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets
Pharmacol. Rev.,
March 1, 2009;
61(1):
9 - 38.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Stoilov, C.-H. Lin, R. Damoiseaux, J. Nikolic, and D. L. Black
A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators
PNAS,
August 12, 2008;
105(32):
11218 - 11223.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. V. Pierre, Y. Sottejeau, J.-M. Gourbeau, G. Sanchez, A. Shidyak, and G. Blanco
Isoform specificity of Na-K-ATPase-mediated ouabain signaling
Am J Physiol Renal Physiol,
April 1, 2008;
294(4):
F859 - F866.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A. Newman, P. Yang, A. D. Pawlus, and K. I. Block
Cardiac Glycosides as Novel Cancer Therapeutic Agents
Mol. Interv.,
February 1, 2008;
8(1):
36 - 49.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Cai, L. Wu, W. Qu, D. Malhotra, Z. Xie, J. I. Shapiro, and J. Liu
Regulation of apical NHE3 trafficking by ouabain-induced activation of the basolateral Na+-K+-ATPase receptor complex
Am J Physiol Cell Physiol,
February 1, 2008;
294(2):
C555 - C563.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Liu, X. Zhao, S. V. Pierre, and A. Askari
Association of PI3K-Akt signaling pathway with digitalis-induced hypertrophy of cardiac myocytes
Am J Physiol Cell Physiol,
November 1, 2007;
293(5):
C1489 - C1497.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Khundmiri, V. Amin, J. Henson, J. Lewis, M. Ameen, M. J. Rane, and N. A. Delamere
Ouabain stimulates protein kinase B (Akt) phosphorylation in opossum kidney proximal tubule cells through an ERK-dependent pathway
Am J Physiol Cell Physiol,
September 1, 2007;
293(3):
C1171 - C1180.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Schoner and G. Scheiner-Bobis
Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth
Am J Physiol Cell Physiol,
August 1, 2007;
293(2):
C509 - C536.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Kaunitz
Reply to Blaustein et al.
Am J Physiol Renal Physiol,
July 1, 2007;
293(1):
F439 - F439.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Liang, J. Tian, L. Liu, S. Pierre, J. Liu, J. Shapiro, and Z.-J. Xie
Identification of a Pool of Non-pumping Na/K-ATPase
J. Biol. Chem.,
April 6, 2007;
282(14):
10585 - 10593.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Pasdois, C. L. Quinlan, A. Rissa, L. Tariosse, B. Vinassa, A. D. T. Costa, S. V. Pierre, P. Dos Santos, and K. D. Garlid
Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS
Am J Physiol Heart Circ Physiol,
March 1, 2007;
292(3):
H1470 - H1478.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. V. Pierre, C. Yang, Z. Yuan, J. Seminerio, C. Mouas, K. D. Garlid, P. Dos-Santos, and Z. Xie
Ouabain triggers preconditioning through activation of the Na+,K+-ATPase signaling cascade in rat hearts
Cardiovasc Res,
February 1, 2007;
73(3):
488 - 496.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Elkareh, D. J. Kennedy, B. Yashaswi, S. Vetteth, A. Shidyak, E. G. R. Kim, S. Smaili, S. M. Periyasamy, I. M. Hariri, L. Fedorova, et al.
Marinobufagenin Stimulates Fibroblast Collagen Production and Causes Fibrosis in Experimental Uremic Cardiomyopathy
Hypertension,
January 1, 2007;
49(1):
215 - 224.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Khundmiri, M. A. Metzler, M. Ameen, V. Amin, M. J. Rane, and N. A. Delamere
Ouabain induces cell proliferation through calcium-dependent phosphorylation of Akt (protein kinase B) in opossum kidney proximal tubule cells
Am J Physiol Cell Physiol,
December 1, 2006;
291(6):
C1247 - C1257.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. J. Kennedy, S. Vetteth, M. Xie, S. M. Periyasamy, Z. Xie, C. Han, V. Basrur, K. Mutgi, V. Fedorov, D. Malhotra, et al.
Ouabain decreases sarco(endo)plasmic reticulum calcium ATPase activity in rat hearts by a process involving protein oxidation
Am J Physiol Heart Circ Physiol,
December 1, 2006;
291(6):
H3003 - H3011.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. C. Thundathil, M. Anzar, and M. M. Buhr
Na+/K+ATPase as a Signaling Molecule During Bovine Sperm Capacitation
Biol Reprod,
September 1, 2006;
75(3):
308 - 317.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Liang, T. Cai, J. Tian, W. Qu, and Z.-J. Xie
Functional Characterization of Src-interacting Na/K-ATPase Using RNA Interference Assay
J. Biol. Chem.,
July 14, 2006;
281(28):
19709 - 19719.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Frese, M. Frese-Schaper, A.-C. Andres, D. Miescher, B. Zumkehr, and R. A. Schmid
Cardiac Glycosides Initiate Apo2L/TRAIL-Induced Apoptosis in Non-Small Cell Lung Cancer Cells by Up-regulation of Death Receptors 4 and 5
Cancer Res.,
June 1, 2006;
66(11):
5867 - 5874.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. D. Kaunitz
Membrane transport proteins: not just for transport anymore
Am J Physiol Renal Physiol,
May 1, 2006;
290(5):
F995 - F996.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Oweis, L. Wu, P. R. Kiela, H. Zhao, D. Malhotra, F. K. Ghishan, Z. Xie, J. I. Shapiro, and J. Liu
Cardiac glycoside downregulates NHE3 activity and expression in LLC-PK1 cells
Am J Physiol Renal Physiol,
May 1, 2006;
290(5):
F997 - F1008.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Ferrari, M. Ferrandi, G. Valentini, and G. Bianchi
Rostafuroxin: an ouabain antagonist that corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension
Am J Physiol Regulatory Integrative Comp Physiol,
March 1, 2006;
290(3):
R529 - R535.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Plourde and S. P. Soltoff
Ouabain potentiates the activation of ERK1/2 by carbachol in parotid gland epithelial cells; inhibition of ERK1/2 reduces Na+-K+-ATPase activity
Am J Physiol Cell Physiol,
March 1, 2006;
290(3):
C702 - C710.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. J. Kennedy, S. Vetteth, S. M. Periyasamy, M. Kanj, L. Fedorova, S. Khouri, M. B. Kahaleh, Z. Xie, D. Malhotra, N. I. Kolodkin, et al.
Central Role for the Cardiotonic Steroid Marinobufagenin in the Pathogenesis of Experimental Uremic Cardiomyopathy
Hypertension,
March 1, 2006;
47(3):
488 - 495.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Cantin, G. Bilodeau, C. Ouellet, J. Liao, and J. W. Hanrahan
Oxidant stress suppresses CFTR expression
Am J Physiol Cell Physiol,
January 1, 2006;
290(1):
C262 - C270.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Tian, T. Cai, Z. Yuan, H. Wang, L. Liu, M. Haas, E. Maksimova, X.-Y. Huang, and Z.-J. Xie
Binding of Src to Na+/K+-ATPase Forms a Functional Signaling Complex
Mol. Biol. Cell,
January 1, 2006;
17(1):
317 - 326.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Wasserstrom and G. L. Aistrup
Digitalis: new actions for an old drug
Am J Physiol Heart Circ Physiol,
November 1, 2005;
289(5):
H1781 - H1793.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Yuan, T. Cai, J. Tian, A. V. Ivanov, D. R. Giovannucci, and Z. Xie
Na/K-ATPase Tethers Phospholipase C and IP3 Receptor into a Calcium-regulatory Complex
Mol. Biol. Cell,
September 1, 2005;
16(9):
4034 - 4045.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. H. Kaplan
A Moving New Role for the Sodium Pump in Epithelial Cells and Carcinomas
Sci. Signal.,
June 21, 2005;
2005(289):
pe31 - pe31.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. K. Scheidenhelm, J. Cresswell, C. A. Haipek, T. P. Fleming, R. W. Mercer, and D. H. Gutmann
Akt-Dependent Cell Size Regulation by the Adhesion Molecule on Glia Occurs Independently of Phosphatidylinositol 3-Kinase and Rheb Signaling
Mol. Cell. Biol.,
April 15, 2005;
25(8):
3151 - 3162.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Kometiani, L. Liu, and A. Askari
Digitalis-Induced Signaling by Na+/K+-ATPase in Human Breast Cancer Cells
Mol. Pharmacol.,
March 1, 2005;
67(3):
929 - 936.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Dong, Q. Li, S.-c. Lyu, A. M. Krensky, and C. Clayberger
A novel apoptosis pathway activated by the carboxyl terminus of p21
Blood,
February 1, 2005;
105(3):
1187 - 1194.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. A. Akimova, A. Y. Bagrov, O. D. Lopina, A. V. Kamernitsky, J. Tremblay, P. Hamet, and S. N. Orlov
Cardiotonic Steroids Differentially Affect Intracellular Na+ and [Na+]i/[K+]i-independent Signaling in C7-MDCK Cells
J. Biol. Chem.,
January 7, 2005;
280(1):
832 - 839.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Y. Xu, E. Takimoto, G. J. Juang, Q. Zhang, H. Rohde, and A. C. Myers
Evidence that the H1-H2 domain of {alpha}1 subunit of (Na++K+)-ATPase participates in the regulation of cardiac contraction
FASEB J,
January 1, 2005;
19(1):
53 - 61.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Dworschak, D. Breukelmann, and J. D. Hannon
The Impact of Isoflurane During Simulated Ischemia/Reoxygenation on Intracellular Calcium, Contractile Function, and Arrhythmia in Ventricular Myocytes
Anesth. Analg.,
November 1, 2004;
99(5):
1302 - 1307.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. C. Barbato, S. Rashid, P. J. Mulrow, J. I. Shapiro, and R. Franco-Saenz
Mechanisms for Aldosterone and Spironolactone-Induced Positive Inotropic Actions in the Rat Heart
Hypertension,
November 1, 2004;
44(5):
751 - 757.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Ferrandi, I. Molinari, P. Barassi, E. Minotti, G. Bianchi, and P. Ferrari
Organ Hypertrophic Signaling within Caveolae Membrane Subdomains Triggered by Ouabain and Antagonized by PST 2238
J. Biol. Chem.,
August 6, 2004;
279(32):
33306 - 33314.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Wang, M. Haas, M. Liang, T. Cai, J. Tian, S. Li, and Z. Xie
Ouabain Assembles Signaling Cascades through the Caveolar Na+/K+-ATPase
J. Biol. Chem.,
April 23, 2004;
279(17):
17250 - 17259.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. G. Reich, S. E. Mason, and B. E. Alger
Novel Form of LTD Induced by Transient, Partial Inhibition of the Na,K-Pump in Rat Hippocampal CA1 Cells
J Neurophysiol,
January 1, 2004;
91(1):
239 - 247.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Abramowitz, C. Dai, K. K. Hirschi, R. I. Dmitrieva, P. A. Doris, L. Liu, and J. C. Allen
Ouabain- and Marinobufagenin-Induced Proliferation of Human Umbilical Vein Smooth Muscle Cells and a Rat Vascular Smooth Muscle Cell Line, A7r5
Circulation,
December 16, 2003;
108(24):
3048 - 3053.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Liu and J. I. Shapiro
Endocytosis and Signal Transduction: Basic Science Update
Biol Res Nurs,
October 1, 2003;
5(2):
117 - 128.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. Xie and T. Cai
Na+-K+-ATPase-Mediated Signal Transduction: From Protein Interaction to Cellular Function
Mol. Interv.,
May 1, 2003;
3(3):
157 - 168.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Baudouin-Legros, F. Brouillard, D. Tondelier, A. Hinzpeter, and A. Edelman
Effect of ouabain on CFTR gene expression in human Calu-3 cells
Am J Physiol Cell Physiol,
March 1, 2003;
284(3):
C620 - C626.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Kennedy, E. Omran, S. M. Periyasamy, J. Nadoor, A. Priyadarshi, J. C. Willey, D. Malhotra, Z. Xie, and J. I. Shapiro
Effect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the Rat
J. Am. Soc. Nephrol.,
January 1, 2003;
14(1):
90 - 97.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Nishio, S. W. Ruch, and J. A. Wasserstrom
Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions
Am J Physiol Heart Circ Physiol,
November 1, 2002;
283(5):
H2045 - H2053.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Taurin, N. O Dulin, D. Pchejetski, R. Grygorczyk, J. Tremblay, P. Hamet, and S. N Orlov
c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: evidence for an intracellular-sodium-mediated, calcium-independent mechanism
J. Physiol.,
September 15, 2002;
543(3):
835 - 847.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. I. Dmitrieva and P. A. Doris
Cardiotonic Steroids: Potential Endogenous Sodium Pump Ligands with Diverse Function
Experimental Biology and Medicine,
September 1, 2002;
227(8):
561 - 569.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Kajikawa, S. Fujimoto, Y. Tsuura, E. Mukai, T. Takeda, Y. Hamamoto, M. Takehiro, J. Fujita, Y. Yamada, and Y. Seino
Ouabain Suppresses Glucose-Induced Mitochondrial ATP Production and Insulin Release by Generating Reactive Oxygen Species in Pancreatic Islets
Diabetes,
August 1, 2002;
51(8):
2522 - 2529.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Haas, H. Wang, J. Tian, and Z. Xie
Src-mediated Inter-receptor Cross-talk between the Na+/K+-ATPase and the Epidermal Growth Factor Receptor Relays the Signal from Ouabain to Mitogen-activated Protein Kinases
J. Biol. Chem.,
May 17, 2002;
277(21):
18694 - 18702.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Rajasekaran, L. G. Palmer, S. Y. Moon, A. Peralta Soler, G. L. Apodaca, J. F. Harper, Y. Zheng, and A. K. Rajasekaran
Na,K-ATPase Activity Is Required for Formation of Tight Junctions, Desmosomes, and Induction of Polarity in Epithelial Cells
Mol. Biol. Cell,
December 1, 2001;
12(12):
3717 - 3732.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Aydemir-Koksoy, J. Abramowitz, and J. C. Allen
Ouabain-induced Signaling and Vascular Smooth Muscle Cell Proliferation
J. Biol. Chem.,
November 30, 2001;
276(49):
46605 - 46611.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Mohammadi, P. Kometiani, Z. Xie, and A. Askari
Role of Protein Kinase C in the Signal Pathways That Link Na+/K+-ATPase to ERK1/2
J. Biol. Chem.,
November 2, 2001;
276(45):
42050 - 42056.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Tian, X. Gong, and Z. Xie
Signal-transducing function of Na+-K+-ATPase is essential for ouabain's effect on [Ca2+]i in rat cardiac myocytes
Am J Physiol Heart Circ Physiol,
November 1, 2001;
281(5):
H1899 - H1907.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Manzerra, M. M. Behrens, L. M. T. Canzoniero, X. Q. Wang, V. Heidinger, T. Ichinose, S. P. Yu, and D. W. Choi
Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity
PNAS,
September 25, 2001;
98(20):
11055 - 11061.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Haas, A. Askari, and Z. Xie
Involvement of Src and Epidermal Growth Factor Receptor in the Signal-transducing Function of Na+/K+-ATPase
J. Biol. Chem.,
September 1, 2000;
275(36):
27832 - 27837.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|