Progress in pathophysiology and related drug development of hypoxia-inducible factor-1

FENG Shijie; MA Xiujuan; ZONG Ying; MAO Yu; ZHANG Xiaodong; GONG Xuelian; ZHANG Xiaofang; LU Guocai

doi:10.3969/j.issn.1006-0111.2014.03.001

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2014 > 32(3): 161-166

FENG Shijie, MA Xiujuan, ZONG Ying, MAO Yu, ZHANG Xiaodong, GONG Xuelian, ZHANG Xiaofang, LU Guocai. Progress in pathophysiology and related drug development of hypoxia-inducible factor-1[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001

Citation:

FENG Shijie, MA Xiujuan, ZONG Ying, MAO Yu, ZHANG Xiaodong, GONG Xuelian, ZHANG Xiaofang, LU Guocai. Progress in pathophysiology and related drug development of hypoxia-inducible factor-1[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(3): 161-166. doi: 10.3969/j.issn.1006-0111.2014.03.001

Progress in pathophysiology and related drug development of hypoxia-inducible factor-1

doi: 10.3969/j.issn.1006-0111.2014.03.001

Department of Health Toxicology, Second Military Medical University, Shanghai 200433, China

Received Date: 2013-03-19
Rev Recd Date: 2013-10-18

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a critical nuclear transcriptional factor mediating cell adaptive response to hypoxia in mammalian and human. It is the key mediator which modulates oxygen homeostasis exclusively. In the one hand, HIF-1 can protect and promote kinds of physiological processes, such as embryo normal development, cartilage and bone formation. In the other hand, it is also involved in lots of human deceases which is caused by ischemia and hypoxia, such as tumor, diabetes and its complications. The molecular mechanisms of HIF-1 involved in these diseases have become a research hotspot and such studies will provide the new therapeutic means for these diseases, recent new drug researches have been focused on HIF-1 related signal pathway inhibitors, HIF-1 activity inhibitors, HIF-1 targeted therapy, etc.
- hypoxia-inducible factor-1,
- hypoxia-response element,
- oxygen homeostasis,
- activity regulation,
- inhibitor

References

[1]	Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation[J]. Mol Cell Biol, 1992, 12(12): 5447-5454.
[2]	Duval E, Ieclercq S, Elissalde JM, et al. Hypoxia-inducible factor 1alpha inhibits the fibroblast like rmrkers typeⅠand type Ⅲ collagen during hypoxia-induced chondrocyte redifferentiation:hypoxia not only induces type collagen and aggrecan,but it a1so inhibits typeⅠand type Ⅲ collagen in the hypoxia-indudble factor 1alpha-dependent redifferentiation of chondrocytes[J]. Arthr Rheum, 2009, 60(10): 3038-3048.
[3]	Lee YK, Kim EJ, Lee JE, et al. Hypoxia induces connective tissue growth factor mRNA expression[J]. J Korean Med Sci, 2009, 24(Suppl): S176-S182.
[4]	Li L, Madu CO, Lu A, et al. HIF-1 alpha promotes a hypoxia-independent cell migration[J]. Open Biol J, 2010, 3(1): 8-14.
[5]	Uniacke J, Holterman CE, Lachance G, et al. An oxygen-regulated switch in the protein synthesis machinery[J]. Nature, 2012, 486(7401):126-129.
[6]	Yoon D, Ponka P, Prchal JT. Hypoxia and hematopoiesis[J]. Am J Physiol Cell Physiol, 2011, 300(6): C1215-C1223.
[7]	Saito T, Fukai A, Mabuchi A, et al. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development[J]. Nat Med, 2010, 16(6):678-686.
[8]	Pelletier J, Dayan F, Durivault J, et al. The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression of the p53-p21 axis[J]. Oncogene, 2012, 31(24):2989-3001.
[9]	Glotzer DJ, Zelzer E, Olsen BR. Impaired skin and hair follicle development in Runx2 deficient mice[J]. Dev Biol, 2008, 315(2): 459-473.
[10]	Yuan LB, Dong HL, Zhang HP,et al. Neuroprotective effect of orexin-A is mediated by an increase of hypoxia-inducible factor-1 activity in rat [J]. Anesthesiology, 2011, 114(2): 340-354.
[11]	Du F, Wu XM, Gong Q, et al. Hyperthermia conditioned astrocyte-cultured medium protects neurons from ischemic injury by the up-regulation of HIF-l alpha and the increased anti-apoptotic ability [J]. Eur J Pharmacol, 2011, 666(1):19-26.
[12]	Eckle T, Kehler D, Lehmann R, et al. Hypoxia-inducible factor-1 is central to cardioprotection:a new paradigm for ischemic Preconditioning[J]. Circulation, 2008, 118(2): 166-175.
[13]	Resar JR, Roguin A, Voner J. et al. Hypoxia-inducible factor-1 alpha polymorphism and coronary collaterals in patients with ischemic heart disease[J]. Chest,2005,128(2): 787-791.
[14]	Rohwer N, Dame C, Haugstelter A, et al. Hypoxia-inducible factor l alpha determines gastric cancer chemosensitivity via modulation of p53 and NF kappaB[J]. PLOS One,20l0, 5(8): e12038-e12045.
[15]	Cai Z, Zhong H, Bosch-Marce M, et al. Complete loss of ischaemic preconditioning induced cardioprotection in mice with partial deficiency of HIF-1α[J]. Cardiovas Res, 2008, 77(3): 463-470.
[16]	Ellis L, Hammers H, Pili R. Targeting tumor angiogenesis with histone deacetylase inhibitors[J].Cancer Lett, 2009, 280(2): 145-152.
[17]	Wang Y, Liu Y, Malek SN, et al. Targeting HIF-1α eliminates cancer stem cells in hematological malignancies[J].Cell Stem Cell, 2011, 8(4): 399-411.
[18]	Mak P, Leav I, Pursell B, et al. ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading[J].Cancer Cell, 2010, 17(4):319-332.
[19]	Luo W, Hu H, Chang R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1[J].Cell, 2011, 145(5): 732-744.
[20]	Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics[J].Oncogene, 2010, 29(5): 625-634.
[21]	Rey S, Semenza GL. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodeling[J].Cardiovase Res, 2010, 86(2): 236-242.
[22]	Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress[J].Mol Cell, 2010, 40(2): 294-309.
[23]	Shimoda LA, Semenza GL. HIF and the lung: role of hypoxia inducible factors in pulmonary development and disease[J].Respi Crit Care Med, 2011, 183(2): 152-156.
[24]	Gartner V, Eigentler TK. Pathogenesis of diabetic macro-and microangiopathy[J].Clin Nephrol, 2008, 70(1): 1-9.
[25]	Sumual S, Saad S, Tang O, et al. Differential regulation of Snail by hypoxia and hyperglycemia in human proximal tubule cells[J].Int J Biochem Cell Biol, 2010, 42(10): 1689-1697.
[26]	Madsen-Bouterse SA, Kowluru RA. Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives[J].Rev Endocr Metab Disord, 2008, 9(4): 315-327.
[27]	Takiyama Y, Harumi T, Watanable J, et al. Tubular injury in a rat model of type 2 diabetes is prevented by metformin: a possible role of HIF-lα expression and oxygen metabolism[J].Diabetes, 2011, 60(3): 981-992.
[28]	Leon GF, Jill TN. Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics, progression of renal disease[J].Kidney lnt, 2008, 74(7): 867-872.
[29]	Zhang H, Qian DZ, Tan YS, et al. Digoxin and other cardiac glycosides inhibit HIF-l alpha synthesis and block tumor growth[J].Proc Natl Acad Sci USA, 2008, 105(50): 19579-19586.
[30]	Hsieh AC, Liu Y, Edlind MP, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis[J].Nature,2012, 485(7396):55-61.
[31]	Wysocki PJ. mTOR in renal cell cancer: modulator of tumor biology and therapeutic target[J].Expert Rev Mol Diagn, 2009, 9(3): 231-241.
[32]	Choi YJ, Rho JK, Lee SJ, et al. HIF-1alpha modulation by topoisomerase inhibitors in non-small cell lung cancer cell lines[J].J Cancer Res Clin Oncol, 2009, 135(8): 1047-1053.
[33]	Kourtis N, Nikoletopoulou V, Tavernarakis N. Small heat-shock proteins protect from heat-stroke-associated neurodegeneration[J].Nature, 2012, 490(7419), 213-218.
[34]	Ruan H, Wang J,Hu L,et al. Killing of brain tumor cells by hypoxia-responsive element mediated expression of BAX[J].Neoplasia, 1999, 1(5):431-437.

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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

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Progress in pathophysiology and related drug development of hypoxia-inducible factor-1

Department of Health Toxicology, Second Military Medical University, Shanghai 200433, China

Received Date: 2013-03-19

Rev Recd Date: 2013-10-18

Key words:

Abstract: Hypoxia-inducible factor-1 (HIF-1) is a critical nuclear transcriptional factor mediating cell adaptive response to hypoxia in mammalian and human. It is the key mediator which modulates oxygen homeostasis exclusively. In the one hand, HIF-1 can protect and promote kinds of physiological processes, such as embryo normal development, cartilage and bone formation. In the other hand, it is also involved in lots of human deceases which is caused by ischemia and hypoxia, such as tumor, diabetes and its complications. The molecular mechanisms of HIF-1 involved in these diseases have become a research hotspot and such studies will provide the new therapeutic means for these diseases, recent new drug researches have been focused on HIF-1 related signal pathway inhibitors, HIF-1 activity inhibitors, HIF-1 targeted therapy, etc.

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Reference (34)

[1]	Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation[J]. Mol Cell Biol, 1992, 12(12): 5447-5454.
[2]	Duval E, Ieclercq S, Elissalde JM, et al. Hypoxia-inducible factor 1alpha inhibits the fibroblast like rmrkers typeⅠand type Ⅲ collagen during hypoxia-induced chondrocyte redifferentiation:hypoxia not only induces type collagen and aggrecan,but it a1so inhibits typeⅠand type Ⅲ collagen in the hypoxia-indudble factor 1alpha-dependent redifferentiation of chondrocytes[J]. Arthr Rheum, 2009, 60(10): 3038-3048.
[3]	Lee YK, Kim EJ, Lee JE, et al. Hypoxia induces connective tissue growth factor mRNA expression[J]. J Korean Med Sci, 2009, 24(Suppl): S176-S182.
[4]	Li L, Madu CO, Lu A, et al. HIF-1 alpha promotes a hypoxia-independent cell migration[J]. Open Biol J, 2010, 3(1): 8-14.
[5]	Uniacke J, Holterman CE, Lachance G, et al. An oxygen-regulated switch in the protein synthesis machinery[J]. Nature, 2012, 486(7401):126-129.
[6]	Yoon D, Ponka P, Prchal JT. Hypoxia and hematopoiesis[J]. Am J Physiol Cell Physiol, 2011, 300(6): C1215-C1223.
[7]	Saito T, Fukai A, Mabuchi A, et al. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development[J]. Nat Med, 2010, 16(6):678-686.
[8]	Pelletier J, Dayan F, Durivault J, et al. The asparaginyl hydroxylase factor-inhibiting HIF is essential for tumor growth through suppression of the p53-p21 axis[J]. Oncogene, 2012, 31(24):2989-3001.
[9]	Glotzer DJ, Zelzer E, Olsen BR. Impaired skin and hair follicle development in Runx2 deficient mice[J]. Dev Biol, 2008, 315(2): 459-473.
[10]	Yuan LB, Dong HL, Zhang HP,et al. Neuroprotective effect of orexin-A is mediated by an increase of hypoxia-inducible factor-1 activity in rat [J]. Anesthesiology, 2011, 114(2): 340-354.
[11]	Du F, Wu XM, Gong Q, et al. Hyperthermia conditioned astrocyte-cultured medium protects neurons from ischemic injury by the up-regulation of HIF-l alpha and the increased anti-apoptotic ability [J]. Eur J Pharmacol, 2011, 666(1):19-26.
[12]	Eckle T, Kehler D, Lehmann R, et al. Hypoxia-inducible factor-1 is central to cardioprotection:a new paradigm for ischemic Preconditioning[J]. Circulation, 2008, 118(2): 166-175.
[13]	Resar JR, Roguin A, Voner J. et al. Hypoxia-inducible factor-1 alpha polymorphism and coronary collaterals in patients with ischemic heart disease[J]. Chest,2005,128(2): 787-791.
[14]	Rohwer N, Dame C, Haugstelter A, et al. Hypoxia-inducible factor l alpha determines gastric cancer chemosensitivity via modulation of p53 and NF kappaB[J]. PLOS One,20l0, 5(8): e12038-e12045.
[15]	Cai Z, Zhong H, Bosch-Marce M, et al. Complete loss of ischaemic preconditioning induced cardioprotection in mice with partial deficiency of HIF-1α[J]. Cardiovas Res, 2008, 77(3): 463-470.
[16]	Ellis L, Hammers H, Pili R. Targeting tumor angiogenesis with histone deacetylase inhibitors[J].Cancer Lett, 2009, 280(2): 145-152.
[17]	Wang Y, Liu Y, Malek SN, et al. Targeting HIF-1α eliminates cancer stem cells in hematological malignancies[J].Cell Stem Cell, 2011, 8(4): 399-411.
[18]	Mak P, Leav I, Pursell B, et al. ERbeta impedes prostate cancer EMT by destabilizing HIF-1alpha and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading[J].Cancer Cell, 2010, 17(4):319-332.
[19]	Luo W, Hu H, Chang R, et al. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1[J].Cell, 2011, 145(5): 732-744.
[20]	Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics[J].Oncogene, 2010, 29(5): 625-634.
[21]	Rey S, Semenza GL. Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodeling[J].Cardiovase Res, 2010, 86(2): 236-242.
[22]	Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress[J].Mol Cell, 2010, 40(2): 294-309.
[23]	Shimoda LA, Semenza GL. HIF and the lung: role of hypoxia inducible factors in pulmonary development and disease[J].Respi Crit Care Med, 2011, 183(2): 152-156.
[24]	Gartner V, Eigentler TK. Pathogenesis of diabetic macro-and microangiopathy[J].Clin Nephrol, 2008, 70(1): 1-9.
[25]	Sumual S, Saad S, Tang O, et al. Differential regulation of Snail by hypoxia and hyperglycemia in human proximal tubule cells[J].Int J Biochem Cell Biol, 2010, 42(10): 1689-1697.
[26]	Madsen-Bouterse SA, Kowluru RA. Oxidative stress and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives[J].Rev Endocr Metab Disord, 2008, 9(4): 315-327.
[27]	Takiyama Y, Harumi T, Watanable J, et al. Tubular injury in a rat model of type 2 diabetes is prevented by metformin: a possible role of HIF-lα expression and oxygen metabolism[J].Diabetes, 2011, 60(3): 981-992.
[28]	Leon GF, Jill TN. Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics, progression of renal disease[J].Kidney lnt, 2008, 74(7): 867-872.
[29]	Zhang H, Qian DZ, Tan YS, et al. Digoxin and other cardiac glycosides inhibit HIF-l alpha synthesis and block tumor growth[J].Proc Natl Acad Sci USA, 2008, 105(50): 19579-19586.
[30]	Hsieh AC, Liu Y, Edlind MP, et al. The translational landscape of mTOR signalling steers cancer initiation and metastasis[J].Nature,2012, 485(7396):55-61.
[31]	Wysocki PJ. mTOR in renal cell cancer: modulator of tumor biology and therapeutic target[J].Expert Rev Mol Diagn, 2009, 9(3): 231-241.
[32]	Choi YJ, Rho JK, Lee SJ, et al. HIF-1alpha modulation by topoisomerase inhibitors in non-small cell lung cancer cell lines[J].J Cancer Res Clin Oncol, 2009, 135(8): 1047-1053.
[33]	Kourtis N, Nikoletopoulou V, Tavernarakis N. Small heat-shock proteins protect from heat-stroke-associated neurodegeneration[J].Nature, 2012, 490(7419), 213-218.
[34]	Ruan H, Wang J,Hu L,et al. Killing of brain tumor cells by hypoxia-responsive element mediated expression of BAX[J].Neoplasia, 1999, 1(5):431-437.

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Progress in pathophysiology and related drug development of hypoxia-inducible factor-1

doi: 10.3969/j.issn.1006-0111.2014.03.001

Abstract

References

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通讯作者: 陈斌, bchen63@163.com

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