Magdalena Millán

Universidad de la República

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Jimena Hochmann

Universidad de la República

Ronell Bologna‐Molina

Universidad de la República

Miguel Arocena

Universidad de la República

José Sotelo‐Silveira

Universidad de la República

Natali D’Aiuto

Universidad de la República

Juan M. Llaguno

Universidad de la República

Ariel Fernández

Universidad de la República

Florencia Lamela

Universidad de la República

Alejandro Silva

Universidad de la República

Felipe Parietti

Universidad de la República

Cooperative Institutions

Universidad de la República

Instituto de Investigaciones Biológicas Clemente Estable

Universidad de Montevideo

Centro Uruguayo de Imagenología Molecular

Universidad La República

University of Buenos Aires

Fundación Ciencias Exactas y Naturales

Consejo Nacional de Investigaciones Científicas y Técnicas

Ministerio de Educación y Cultura

Instituto Nacional de Investigación Agropecuaria

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Author Correction: Hypoxia, acidification and oxidative stress in cells cultured at large distances from an oxygen source

Scientific Reports (2023)

Natali D’Aiuto Jimena Hochmann Magdalena Millán Andrés Di Paolo Ronell Bologna‐Molina

Hypoxia

10.1038/s41598-023-36156-7

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Hypoxia, acidification and oxidative stress in cells cultured at large distances from an oxygen source

Scientific Reports (2022)

Natali D’Aiuto Jimena Hochmann Magdalena Millán Andrés Di Paolo Ronell Bologna‐Molina

Abstract Hypoxia is a condition frequently encountered by cells in tissues, whether as a normal feature of their microenvironment or subsequent to deregulated growth. Hypoxia can lead to acidification and increased oxidative stress, with profound consequences for cell physiology and tumorigenesis. Therefore, the interplay between hypoxia and oxidative stress is an important aspect for understanding the effects of hypoxic microenvironments on cells. We have used a previously developed variant of the method of coverslip-induced hypoxia to study the process of acidification in a hypoxic microenvironment and to simultaneously visualize intracellular levels of hypoxia and oxidative stress. We observed high accumulation of CO 2 in hypoxic conditions, which we show is the main contributor to acidification in our model. Also, increased levels of oxidative stress were observed in moderately hypoxic cells close to the oxygen source, where the mitochondrial membrane potential was preserved. Conversely, cells at large distances from the oxygen source showed higher levels of hypoxia, milder oxidative stress and reduced mitochondrial membrane potential. Our results contribute to characterize the interplay between reduced oxygen levels, acidification and oxidative stress in a simple in vitro setting, which can be used to model cell responses to an altered environment, such as the early tumor microenvironment.

Hypoxia

10.1038/s41598-022-26205-y

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Citations (24)

Mechanical profile of human keratinocytes expressing HPV-18 oncogenes

Biochemical and Biophysical Research Communications (2023)

Magdalena Millán Lihuén Villarreal Natali D’Aiuto Ronell Bologna‐Molina José Sotelo‐Silveira

HaCaT

Malignant Transformation

10.1016/j.bbrc.2023.03.054

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Differential effects of coverslip-induced hypoxia and cobalt chloride mimetic hypoxia on cellular stress, metabolism, and nuclear structure

Tissue and Cell (2024)

Florencia Lamela Ronell Bologna‐Molina Felipe Parietti Vanesa Pereira‐Prado Magdalena Millán

Hypoxia

Cobalt chloride

10.1016/j.tice.2024.102408

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Citations (1)

Contributions of viral oncogenes of HPV-18 and hypoxia to oxidative stress and genetic damage in human keratinocytes

Scientific Reports (2023)

Jimena Hochmann Magdalena Millán Paola Hernández Laura Lafon-Hughes NATALI DI ́AIUTO

Abstract Infection with high-risk human papillomaviruses like HPV-16 and HPV-18 is highly associated with the development of cervical and other cancers. Malignant transformation requires viral oncoproteins E5, E6 and E7, which promote cell proliferation and increase DNA damage. Oxidative stress and hypoxia are also key factors in cervical malignant transformation. Increased levels of reactive species of oxygen (ROS) and nitrogen (RNS) are found in the hypoxic tumor microenvironment, promoting genetic instability and invasiveness. In this work, we studied the combined effect of E5, E6 and E7 and hypoxia in increasing oxidative stress and promoting DNA damage and nuclear architecture alterations. HaCaT cells containing HPV-18 viral oncogenes (HaCaT E5/E6/E7-18) showed higher ROS levels in normoxia and higher levels of RNS in hypoxia compared to HaCaT parental cells, as well as higher genetic damage in hypoxia as measured by γH2AX and comet assays. In hypoxia, HaCaT E5/E6/E7-18 increased its nuclear dry mass and both cell types displayed marked heterogeneity in nuclear dry mass distribution and increased nuclear foci. Our results show contributions of both viral oncogenes and hypoxia to oxidative stress, DNA damage and altered nuclear architecture, exemplifying how an altered microenvironment combines with oncogenic transformation to promote tumor progression.

HaCaT

Hypoxia

Malignant Transformation

10.1038/s41598-023-44880-3

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Citations (6)

Differential cell architecture and microenvironmental responses of pretumoral and tumoral cellular models exposed to coverslip-induced hypoxia

Histochemistry and Cell Biology (2025)

Magdalena Millán Felipe Parietti Florencia Lamela María Cecilia De Rossi Belén Benítez

Hypoxia

10.1007/s00418-024-02350-5

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