Assessment of hypoxia and TNF-alpha response by a vector with HRE and NF-kappaB response elements.
Hypoxia and inflammatory cytokine activation (H&I) are common processes in many acute and chronic diseases. Thus, a single vector that responds to both hypoxia and inflammatory cytokines, such as TNF-alpha, is useful for assesing the severity of such diseases. Adaptation to hypoxia is regulated primarily by hypoxia inducible transcription factor (HIF alpha) nuclear proteins that engage genes containing a hypoxia response element (HRE). Inflammation activates a multitude of cytokines, including TNF-alpha, that invariably modulate activation of the nuclear factor kappa B (NF-kB) transcription factor. We constructed a vector that encompassed both a hypoxia response element (HRE), and a NF-kappaB responsive element. We show that this vector was functionally responsive to both hypoxia and TNF-alpha,in vitroandin vivo. Thus, this vector might be suitable for the detection and assessment of hypoxia or TNF-alpha.
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Zhilin
Z
Chen
Department of Pharmacology, Dalhousie Medicine New Brunswick, PO Box 5050, 100 Tucker Park Road, Saint John, NB, Canada E2L 4L5.
Ashley L
AL
Eadie
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Sean R
SR
Hall
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Laurel
L
Ballantyne
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
David
D
Ademidun
Department of Anatomy and Cell Biology Queen's University, Kingston, Ontario, Canada.
M Yat
MY
Tse
Department of Anatomy and Cell Biology Queen's University, Kingston, Ontario, Canada.
Stephen C
SC
Pang
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Luis G
LG
Melo
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Christopher A
CA
Ward
Department of Pharmacology, Dalhousie Medicine New Brunswick, PO Box 5050, 100 Tucker Park Road, Saint John, NB, Canada E2L 4L5, keith.brunt@dal.ca.
Keith R
KR
Brunt
D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D005822:Genetic Vectors / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020218:Response Elements; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha