Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart

Jin Ming Hwang, Yi Jiun Weng, James A. Lin, Da Tian Bau, Fu Yang Ko, Fuu Jen Tsai, Chang Hai Tsai, Chieh Hsi Wu, Pei Cheng Lin, Chih Yang Huang, Wei Wen Kuo

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1α and Shh. The relationship between HIF-1α and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1α signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1α and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.

Original languageEnglish
Pages (from-to)179-187
Number of pages9
JournalMolecular and Cellular Biochemistry
Volume311
Issue number1-2
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Fingerprint

Rats
Insulin-Like Growth Factor II
Ischemia
Embryonic Structures
Cell culture
Vascular Endothelial Growth Factor A
Fetal Heart
Cell proliferation
Cell Culture Techniques
Compaction
Genes
Chemical activation
Umbilical Cord
Wounds and Injuries
Regulator Genes
Cardiac Myocytes
Signal Transduction
Cell Proliferation
Hypoxia
cyclopamine

Keywords

  • H9c2 cells
  • HIF-1α
  • Hypoxia
  • Ischemia
  • Shh

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hwang, J. M., Weng, Y. J., Lin, J. A., Bau, D. T., Ko, F. Y., Tsai, F. J., ... Kuo, W. W. (2008). Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart. Molecular and Cellular Biochemistry, 311(1-2), 179-187. https://doi.org/10.1007/s11010-008-9708-6

Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart. / Hwang, Jin Ming; Weng, Yi Jiun; Lin, James A.; Bau, Da Tian; Ko, Fu Yang; Tsai, Fuu Jen; Tsai, Chang Hai; Wu, Chieh Hsi; Lin, Pei Cheng; Huang, Chih Yang; Kuo, Wei Wen.

In: Molecular and Cellular Biochemistry, Vol. 311, No. 1-2, 04.2008, p. 179-187.

Research output: Contribution to journalArticle

Hwang, JM, Weng, YJ, Lin, JA, Bau, DT, Ko, FY, Tsai, FJ, Tsai, CH, Wu, CH, Lin, PC, Huang, CY & Kuo, WW 2008, 'Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart', Molecular and Cellular Biochemistry, vol. 311, no. 1-2, pp. 179-187. https://doi.org/10.1007/s11010-008-9708-6
Hwang, Jin Ming ; Weng, Yi Jiun ; Lin, James A. ; Bau, Da Tian ; Ko, Fu Yang ; Tsai, Fuu Jen ; Tsai, Chang Hai ; Wu, Chieh Hsi ; Lin, Pei Cheng ; Huang, Chih Yang ; Kuo, Wei Wen. / Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart. In: Molecular and Cellular Biochemistry. 2008 ; Vol. 311, No. 1-2. pp. 179-187.
@article{a3492969b3ca46599c09aad129859e48,
title = "Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart",
abstract = "Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1α and Shh. The relationship between HIF-1α and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1α signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1α and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.",
keywords = "H9c2 cells, HIF-1α, Hypoxia, Ischemia, Shh",
author = "Hwang, {Jin Ming} and Weng, {Yi Jiun} and Lin, {James A.} and Bau, {Da Tian} and Ko, {Fu Yang} and Tsai, {Fuu Jen} and Tsai, {Chang Hai} and Wu, {Chieh Hsi} and Lin, {Pei Cheng} and Huang, {Chih Yang} and Kuo, {Wei Wen}",
year = "2008",
month = "4",
doi = "10.1007/s11010-008-9708-6",
language = "English",
volume = "311",
pages = "179--187",
journal = "Molecular and Cellular Biochemistry",
issn = "0300-8177",
publisher = "Springer Netherlands",
number = "1-2",

}

TY - JOUR

T1 - Hypoxia-induced compensatory effect as related to Shh and HIF-1α in ischemia embryo rat heart

AU - Hwang, Jin Ming

AU - Weng, Yi Jiun

AU - Lin, James A.

AU - Bau, Da Tian

AU - Ko, Fu Yang

AU - Tsai, Fuu Jen

AU - Tsai, Chang Hai

AU - Wu, Chieh Hsi

AU - Lin, Pei Cheng

AU - Huang, Chih Yang

AU - Kuo, Wei Wen

PY - 2008/4

Y1 - 2008/4

N2 - Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1α and Shh. The relationship between HIF-1α and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1α signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1α and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.

AB - Chronic cardiac ischemia/hypoxia induces coronary collateral formation and cardiomyocyte proliferation. Hypoxia can induce cellular adaptive responses, such as synthesis of VEGF for angiogenesis and IGF-2 for proliferation. Both reduce apoptotic effects to minimize injury or damage. To investigate the mechanism of neoangiogenesis and proliferation of fetal heart under umbilical cord compression situation, we used H9c2 cardiomyoblast cell culture, and in vivo embryonic hearts as our study models. Results showed hypoxia induced not only the increase of IGF-2 and VEGF expression but also the activation of their upstream regulatory genes, HIF-1α and Shh. The relationship between HIF-1α and Shh was further studied by using cyclopamine and 2-ME2, inhibitor of Shh and HIF-1α signaling, respectively, in the cardiomyoblast cell culture under hypoxia. We found that the two inhibitors not only blocked their own signal pathway, but also inhibited each other. The observations revealed when fetal heart under hypoxia that HIF-1α and Shh pathways maybe involve in cell proliferation and neoangiogenesis to minimize injury or damage, whereas the complex cross-talk between the two pathways remains unknown.

KW - H9c2 cells

KW - HIF-1α

KW - Hypoxia

KW - Ischemia

KW - Shh

UR - http://www.scopus.com/inward/record.url?scp=41349117592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41349117592&partnerID=8YFLogxK

U2 - 10.1007/s11010-008-9708-6

DO - 10.1007/s11010-008-9708-6

M3 - Article

C2 - 18228117

AN - SCOPUS:41349117592

VL - 311

SP - 179

EP - 187

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

SN - 0300-8177

IS - 1-2

ER -